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Ma K, Li Y, Wu J, Fu Y, Yin L, Xu S, Weng F, Yao Y, Wang C. Differential Diagnosis Value of Neutrophil Gelatinase Associated Lipocalin as a Noninvasive Biomarker in Perianal Fistulizing Crohn's Disease. J Inflamm Res 2025; 18:4075-4086. [PMID: 40125092 PMCID: PMC11930251 DOI: 10.2147/jir.s504213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 03/04/2025] [Indexed: 03/25/2025] Open
Abstract
Background Diagnosing perianal fistulizing Crohn's disease (pfCD) typically depends on costly and time-intensive endoscopic and radiographic procedures. Compelling evidence indicates that neutrophil gelatinase-associated lipocalin (NGAL) plays a role in the pathophysiology of Crohn's disease (CD) and may serve as a noninvasive biomarker for its diagnosis. This study aimed to evaluate NGAL's potential as a noninvasive diagnostic biomarker between pfCD and cryptoglandular (CG) perianal fistula, and its correlation with disease severity in pfCD. Methods Serum, fecal, and fistula tissue samples were collected from 96 patients with pfCD and 97 patients with CG perianal fistula as controls. Serum NGAL levels were quantified through ELISA and fistula tissue NGAL levels were quantified through immunohistochemical staining, while pfCD disease severity was evaluated using the Crohn's Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI). Additional laboratory parameters, including NGAL, fecal calprotectin (FC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), were analyzed, and their correlations were assessed. Receiver operating characteristic (ROC) analysis was conducted to evaluate NGAL's diagnostic potential for pfCD. Results Levels of serum NGAL, FC, CRP, and ESR in patients with pfCD were significantly elevated compared to the control group (p < 0.001); Spearman correlation analysis indicated a positive correlation between serum NGAL and FC, CRP, ESR, CDAI, and PDAI scores. The area under the ROC curve (AUC) for serum NGAL in diagnosing pfCD was 0.927 (95% CI: 0.890-0.964). The AUC for FC in diagnosing pfCD were 0.887 (95% CI: 0.839-0.935). Additionally, serum and fistula tissue NGAL levels were positively correlated with disease complexity in pfCD according to the Montreal classification. Conclusion These findings suggest that serum NGAL is associated with pfCD severity and may offer a promising noninvasive biomarker for diagnosing and assessing pfCD.
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Affiliation(s)
- Kai Ma
- Department of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
| | - Yikun Li
- Department of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
| | - Jingwen Wu
- Department of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
| | - Yi Fu
- Department of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
| | - Lu Yin
- Department of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
| | - Simin Xu
- Department of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
| | - Feiyang Weng
- Department of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
| | - Yibo Yao
- Department of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
| | - Chen Wang
- Department of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
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Wang J, Tao H, Fan Q, Wang Z, Han B, Wang X, Wang J. Anti-Bacterial and Anti-Inflammatory Properties of Sophoridine and Its Effect on Diarrhea in Mice. Int J Mol Sci 2025; 26:2122. [PMID: 40076745 PMCID: PMC11901078 DOI: 10.3390/ijms26052122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 02/11/2025] [Accepted: 02/25/2025] [Indexed: 03/14/2025] Open
Abstract
To investigate the anti-bacterial and anti-inflammatory properties of sophoridine and elucidate its mechanism of action, we carried out both in vitro and in vivo experiments. Multiple bacterial strains were utilized to determine the effective concentration of sophoridine in antibacterial and bactericidal assays. Subsequently, LPS-stimulated RAW264.7 cells and E. coli-challenged BALB/c mice models were employed to evaluate the production of inflammatory cytokines. Our results showed that sophoridine concentrations exceeding 5.12 mg/mL significantly inhibited cell viability, while 0.32 mg/mL of sophoridine demonstrated the optimal anti-inflammatory activity at 12 h. In E. coli-induced diarrheal mice, doses of 15, 30, and 60 mg/kg BW of sophoridine alleviated fecal occult blood and exhibited anti-inflammatory effects by reducing the level of serum TNF-α, IL-1β, and IL-6 levels, increasing serum IL-10, and inhibiting leucocyte infiltration in the duodenum. Notably, 15 mg/kg BW of sophoridine effectively decreased the mRNA and protein expression of NF-κB p65. These findings suggest that sophoridine has promising potential for the treatment of diarrhea through its anti-inflammatory effects mediated by the inhibition of NF-κB activation.
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Affiliation(s)
- Jiaxue Wang
- Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (J.W.); (H.T.); (Q.F.); (Z.W.); (B.H.)
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, China
- College of Grassland Agriculture, Northwest A&F University, Xianyang 712100, China
| | - Hui Tao
- Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (J.W.); (H.T.); (Q.F.); (Z.W.); (B.H.)
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, China
| | - Qiuyu Fan
- Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (J.W.); (H.T.); (Q.F.); (Z.W.); (B.H.)
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, China
| | - Zhenlong Wang
- Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (J.W.); (H.T.); (Q.F.); (Z.W.); (B.H.)
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, China
| | - Bing Han
- Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (J.W.); (H.T.); (Q.F.); (Z.W.); (B.H.)
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, China
| | - Xiumin Wang
- Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (J.W.); (H.T.); (Q.F.); (Z.W.); (B.H.)
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, China
| | - Jingquan Wang
- Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (J.W.); (H.T.); (Q.F.); (Z.W.); (B.H.)
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, China
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Durham K, Atagozli T, Elliott DE, Ince MN. Laboratory Tests in Inflammatory Bowel Disease: An Evidence-Based Approach to Daily Practice. Biomedicines 2025; 13:491. [PMID: 40002904 PMCID: PMC11852734 DOI: 10.3390/biomedicines13020491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 01/25/2025] [Accepted: 01/30/2025] [Indexed: 02/27/2025] Open
Abstract
Inflammatory bowel diseases (IBDs) comprise a group of chronic gastrointestinal disorders characterized by periods of relapse and remission. The mainstay of treatment is medical, involving medications such as steroids, immune modulators, monoclonal antibodies (categorized as biologics), and small molecules. These medications can provide profound therapeutic benefits, but they can also cause severe and irreversible toxicities. Clinicians may utilize laboratory tests in the diagnosis and management of IBD including assessment of disease activity, monitoring medication response or toxicity, surveillance of infectious complications, and detection of nutritional deficiencies. Routine use of laboratory tests may help clinicians avoid reactivation of life-threatening infections such as tuberculosis or hepatitis B virus upon initiation of immune suppressive therapy. They can also be used to detect vitamin deficiencies such as B12 deficiency, which has the potential to cause irreversible neurologic damage. While some laboratory tests constitute established practices, the utility of newer tests such therapeutic drug monitoring (TDM) in the era of biologics is an evolving topic. Although clinical assessment with imaging, endoscopic, and histopathological examination is standard practice, laboratory tests serve as valuable adjuncts. We aim to explore the broad range of laboratory tests available to clinicians and to summarize their application in the current management of IBD in daily clinical practice, with special attention to updates in therapeutic drug monitoring.
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Affiliation(s)
- Katelin Durham
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA; (K.D.); (D.E.E.)
- Iowa City Veterans Affairs Medical Center, 601 Highway 6 W, Iowa City, IA 52246, USA
| | - Tyler Atagozli
- Carver College of Medicine, University of Iowa, 375 Newton Road, Iowa City, IA 52242, USA;
| | - David E. Elliott
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA; (K.D.); (D.E.E.)
- Iowa City Veterans Affairs Medical Center, 601 Highway 6 W, Iowa City, IA 52246, USA
| | - M. Nedim Ince
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA; (K.D.); (D.E.E.)
- Iowa City Veterans Affairs Medical Center, 601 Highway 6 W, Iowa City, IA 52246, USA
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Nagata M, Inage E, Yamada H, Kudo T, Toriumi S, Sakaguchi K, Tanaka Y, Jimbo K, Ohtsuka Y, Shimizu T. Efficacy of sequential fecal-marker examination for evaluating gastrointestinal inflammation in solid food protein-induced enterocolitis syndrome. Allergol Int 2024; 73:556-562. [PMID: 38749792 DOI: 10.1016/j.alit.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 04/19/2024] [Accepted: 04/24/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND Food protein-induced enterocolitis syndrome caused by solid foods (Solid-FPIES) is a non-immunoglobulin E-mediated allergic disease characterized by delayed gastrointestinal symptoms. An oral food challenge (OFC) test, although necessary, can be inconclusive in cases with mild symptoms. Moreover, limited diagnostic marker availability highlights the need for novel surrogate markers. We aimed to examine the efficacy of fecal hemoglobin (FHb), lactoferrin (FLf), and calprotectin (FCp) over time in evaluating gastrointestinal inflammation degree in Solid-FPIES. METHODS This observational study included 40 patients and 42 episodes at Juntendo University Hospital and affiliated hospitals between October 2020 and March 2024 categorized into FPIES (12 patients with 11 egg yolk, 1 fish, and 1 soybean episodes), control (14 patients with 15 episodes), and remission (14 patients). Fecal tests were performed for 7 days following antigen exposure. The ratios of each value were divided by the baseline value and analyzed over time course. RESULTS The FPIES group had significantly higher peak ratios of all fecal markers than the control group (p < 0.01). The median FHb, FLf, and FCp ratios were 3.25, 9.09, and 9.79 in the FPIES group and 1.08, 1.29, and 1.49 in the control group, respectively. In the remission group, several patients had fluctuating fecal markers despite negative OFC, and one patient was diagnosed with FPIES by OFC with increased load. Receiver operating characteristic curve analyses revealed high diagnostic performance for each fecal marker in FPIES. CONCLUSIONS Sequential fecal marker examination proved valuable in diagnosing Solid-FPIES and evaluating the degree of gastrointestinal inflammation.
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Affiliation(s)
- Masumi Nagata
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Pediatrics, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo, Japan.
| | - Eisuke Inage
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Hiromichi Yamada
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Takahiro Kudo
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Shun Toriumi
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Keita Sakaguchi
- Department of Pediatrics, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo, Japan
| | - Yuko Tanaka
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Pediatrics, Tokyo Rinkai Hospital, Tokyo, Japan
| | - Keisuke Jimbo
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yoshikazu Ohtsuka
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
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Zhou T, Wu J, Khan A, Hu T, Wang Y, Salama ES, Su S, Han H, Jin W, Li X. A probiotic Limosilactobacillus fermentum GR-3 mitigates colitis-associated tumorigenesis in mice via modulating gut microbiome. NPJ Sci Food 2024; 8:61. [PMID: 39242568 PMCID: PMC11379937 DOI: 10.1038/s41538-024-00307-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 08/29/2024] [Indexed: 09/09/2024] Open
Abstract
Bacterial therapy for colorectal cancer (CRC) represents a burgeoning frontier. The probiotic Limosilactobacillus fermentum GR-3, derived from traditional food "Jiangshui", exhibited superior antioxidant capacity by producing indole derivatives ICA and IPA. In an AOM/DSS-induced CRC mouse model, GR-3 treatment alleviated weight loss, colon shortening, rectal bleeding and intestinal barrier disruption by reducing oxidative stress and inflammation. GR-3 colonization in distant colon induced apoptosis and reduced tumor incidence by 51.2%, outperforming the control strain and vitamin C. The beneficial effect of GR-3 on CRC was associated with gut microbiome modulation, increasing SCFA producer Lachnospiraceae NK4A136 group and suppressing pro-inflammatory strain Bacteroides. Metagenomic and metabolic analyses revealed that GR-3 intervention upregulated antioxidant genes (xseA, ALDH) and butyrate synthesis gene (bcd), while increasing beneficial metabolites (SCFAs, ICA, IPA, VB12 and VD3) and reducing harmful secondary bile acids. Overall, GR-3 emerges as a promising candidate in CRC therapy, offering effective gut microbiome remediation.
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Affiliation(s)
- Tuoyu Zhou
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu, 730000, China
- State Key Laboratory of Grassland Agro-ecosystems, College of Pastoral Agricultural Science and Technology, Lanzhou University, Lanzhou, China
| | - Jingyuan Wu
- The First Clinical Medical College of Lanzhou University, Lanzhou University, Lanzhou, 730000, China
| | - Aman Khan
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu, 730000, China
| | - Tianxiang Hu
- Georgia Cancer Center, Augusta University, 1410 Laney Walker Blvd, Augusta, GA, 30912, USA
| | - Yiqing Wang
- The First Clinical Medical College of Lanzhou University, Lanzhou University, Lanzhou, 730000, China
| | - El-Sayed Salama
- Department of Occupational and Environmental Health, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu Province, PR China
| | - Shaochen Su
- Healthy Examination & Management Center, First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Huawen Han
- State Key Laboratory of Grassland Agro-ecosystems, College of Pastoral Agricultural Science and Technology, Lanzhou University, Lanzhou, China.
| | - Weilin Jin
- Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, Lanzhou, China.
| | - Xiangkai Li
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu, 730000, China.
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Prodromou SI, Chatzopoulou F, Saiti A, Giannopoulos-Dimitriou A, Koudoura LA, Pantazaki AA, Chatzidimitriou D, Vasiliou V, Vizirianakis IS. Hepatotoxicity assessment of innovative nutritional supplements based on olive-oil formulations enriched with natural antioxidants. Front Nutr 2024; 11:1388492. [PMID: 38812942 PMCID: PMC11133736 DOI: 10.3389/fnut.2024.1388492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 04/25/2024] [Indexed: 05/31/2024] Open
Abstract
Introduction This study focuses on the assessment of extra virgin olive-oil and olive fruit-based formulations enriched with natural antioxidants as potential nutritional supplements for alleviating symptoms and long-term consequences of illnesses whose molecular pathophysiology is affected by oxidative stress and inflammation, such as Alzheimer's disease (AD). Methods Besides evaluating cell viability and proliferation capacity of human hepatocellular carcinoma HepG2 cells exposed to formulations in culture, hepatotoxicity was also considered as an additional safety measure using quantitative real-time PCR on RNA samples isolated from the cell cultures and applying approaches of targeted molecular analysis to uncover potential pathway effects through gene expression profiling. Furthermore, the formulations investigated in this work contrast the addition of natural extract with chemical forms and evaluate the antioxidant delivery mode on cell toxicity. Results The results indicate minimal cellular toxicity and a significant beneficial impact on metabolic molecular pathways in HepG2 cell cultures, thus paving the way for innovative therapeutic strategies using olive-oil and antioxidants in dietary supplements to minimize the long-term effects of oxidative stress and inflammatory signals in individuals being suffered by disorders like AD. Discussion Overall, the experimental design and the data obtained support the notion of applying innovative molecular methodologies and research techniques to evidently advance the delivery, as well as the scientific impact and validation of nutritional supplements and dietary products to improve public health and healthcare outcomes.
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Affiliation(s)
- Sofia I. Prodromou
- Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Fani Chatzopoulou
- Laboratory of Microbiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Labnet Laboratories, Department of Molecular Biology and Genetics, Thessaloniki, Greece
| | - Aikaterini Saiti
- Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Loukia A. Koudoura
- Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Anastasia A. Pantazaki
- Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Chatzidimitriou
- Laboratory of Microbiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Vasilis Vasiliou
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, United States
| | - Ioannis S. Vizirianakis
- Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Department of Health Sciences, School of Health and Life Sciences, University of Nicosia, Nicosia, Cyprus
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Bourgonje AR, Bourgonje MF, la Bastide-van Gemert S, Nilsen T, Hidden C, Gansevoort RT, Mulder DJ, Hillebrands JL, Bakker SJ, Dullaart RP, van Goor H, Abdulle AE. A Prospective Study of the Association Between Plasma Calprotectin Levels and New-Onset CKD in the General Population. Kidney Int Rep 2024; 9:1265-1275. [PMID: 38707832 PMCID: PMC11068960 DOI: 10.1016/j.ekir.2024.02.1392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 01/08/2024] [Accepted: 02/12/2024] [Indexed: 05/07/2024] Open
Abstract
Introduction Systemic inflammation has been associated with chronic kidney disease (CKD). In this study, we aimed to investigate a potential association between the plasma biomarker of inflammation calprotectin and new-onset CKD in a population-based cohort study. Methods Individuals without CKD at baseline (n = 4662) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) prospective population-based cohort study in the Netherlands were included. Baseline plasma calprotectin levels were assessed in samples that had been stored at -80 °C. Occurrence of new-onset CKD was defined as a composite outcome of an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2, urinary albumin excretion (UAE) >30 mg/24h, or both. Results Baseline median (interquartile range) plasma calprotectin levels were 0.49 (0.35-0.68) mg/l and baseline median eGFR was 95.9 (interquartile range: 85.0-105.7) ml/min per 1.73 m2. After median follow-up of 8.3 (7.8-8.9) years, 467 participants developed new-onset CKD. Baseline plasma calprotectin levels were significantly associated with an increased risk of new-onset CKD (hazard ratio [HR] per doubling 1.28 [95% confidence interval, CI: 1.14-1.44], P < 0.001), independent of potentially confounding factors (HR 1.14 [95% CI: 1.01-1.29], P = 0.034), except for baseline high-sensitive C-reactive protein (hs-CRP) (HR 1.05 [0.91-1.21], P = 0.494). In secondary analyses, the association between plasma calprotectin and occurrence of UAE >30 mg/24h remained significant (HR 1.17 [1.02-1.34], P = 0.027), but not significantly so for the incidence of eGFR <60 ml/min per 1.73 m2 as individual outcome (HR 1.15 [0.92-1.43], P = 0.218). Conclusion Higher plasma calprotectin levels are associated with an increased risk of developing CKD in the general population. This association is mitigated after adjustment for hs-CRP, and more pronounced with new-onset CKD defined by UAE.
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Affiliation(s)
- Arno R. Bourgonje
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Martin F. Bourgonje
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Sacha la Bastide-van Gemert
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | | | | | - Ron T. Gansevoort
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Douwe J. Mulder
- Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Jan-Luuk Hillebrands
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Stephan J.L. Bakker
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Robin P.F. Dullaart
- Department of Internal Medicine, Division of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Harry van Goor
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Amaal E. Abdulle
- Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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Kumar SE, Jaleel R, Varghese T, Praharaj I, Benny S, Chowdhury SD, Thomas R, Simon E, Joseph AJ, Dutta AK. Fecal calgranulin as a potential screening tool to differentiate inflammatory bowel disease from irritable bowel syndrome. Indian J Gastroenterol 2024; 43:264-266. [PMID: 38261246 DOI: 10.1007/s12664-024-01525-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2024]
Affiliation(s)
- Santhosh E Kumar
- Department of Hepatology, Christian Medical College, Vellore, 632 004, India
| | - Rajeeb Jaleel
- Department of Gastroenterology, Christian Medical College, Vellore, A Block, 7th Floor, Ranipet Campus, Kilminnal, Ranipet, 632 517, India
| | - Tintu Varghese
- Wellcome Research Unit, Christian Medical College, Vellore, 632 004, India
| | - Ira Praharaj
- Wellcome Research Unit, Christian Medical College, Vellore, 632 004, India
| | - Stephan Benny
- Department of Gastroenterology, Christian Medical College, Vellore, A Block, 7th Floor, Ranipet Campus, Kilminnal, Ranipet, 632 517, India
| | - Sudipta D Chowdhury
- Department of Gastroenterology, Christian Medical College, Vellore, A Block, 7th Floor, Ranipet Campus, Kilminnal, Ranipet, 632 517, India
| | - Reuben Thomas
- Department of Gastroenterology, Christian Medical College, Vellore, A Block, 7th Floor, Ranipet Campus, Kilminnal, Ranipet, 632 517, India
| | - Ebby Simon
- Department of Gastroenterology, Christian Medical College, Vellore, A Block, 7th Floor, Ranipet Campus, Kilminnal, Ranipet, 632 517, India
| | - A J Joseph
- Department of Gastroenterology, Christian Medical College, Vellore, A Block, 7th Floor, Ranipet Campus, Kilminnal, Ranipet, 632 517, India
| | - Amit Kumar Dutta
- Department of Gastroenterology, Christian Medical College, Vellore, A Block, 7th Floor, Ranipet Campus, Kilminnal, Ranipet, 632 517, India.
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Bourgonje AR, Bourgonje MF, la Bastide‐van Gemert S, Nilsen T, Hidden C, Gansevoort RT, Bakker SJL, Mulder DJ, Dullaart RPF, Abdulle AE, van Goor H. Plasma Calprotectin Levels Associate With New-Onset Hypertension in the General Population: A Prospective Cohort Study. J Am Heart Assoc 2024; 13:e031458. [PMID: 38156449 PMCID: PMC10863804 DOI: 10.1161/jaha.123.031458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 11/03/2023] [Indexed: 12/30/2023]
Abstract
BACKGROUND Low-grade systemic inflammation is a relevant pathogenic mechanism underlying the development of hypertension. In this study, we hypothesized that plasma calprotectin levels, as a biomarker of neutrophil-mediated inflammation, is associated with developing new-onset hypertension in the general population. METHODS AND RESULTS Plasma calprotectin levels were determined in 3524 participants who participated in the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study, a prospective population-based cohort study. Plasma calprotectin levels were studied for associations with the risk of new-onset hypertension, defined as systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or the first recorded use of antihypertensives. Participants with hypertension at baseline were excluded. Median plasma calprotectin levels were 0.48 (0.34-0.66) mg/L, and median systolic blood pressure was 117 (109-126) mm Hg. Plasma calprotectin levels were significantly associated with the risk of new-onset hypertension (hazard ratio [HR], per doubling 1.30 [95% CI, 1.21-1.41]; P<0.001), also after adjustment for age and sex (HR, 1.26 [95% CI, 1.16-1.37]; P<0.001), but not after additional adjustment for potentially confounding factors, including baseline systolic blood pressure (HR, 1.00 [95% CI, 0.90-1.11]; P=0.996). Stratified analyses showed significant effect modification by sex (Pinteraction=0.023) and urinary albumin excretion (Pinteraction=0.004), with higher HRs in men (compared with women) and in individuals with higher urinary albumin excretion (>9.3 mg per 24 hours) compared with lower urinary albumin excretion (≤9.3 mg per 24 hours). CONCLUSIONS Higher plasma calprotectin levels are associated with an increased risk of new-onset hypertension in the general population. This association is dependent on baseline systolic blood pressure and is particularly prominent in men compared with women.
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Affiliation(s)
- Arno R. Bourgonje
- Department of Gastroenterology and HepatologyUniversity of Groningen, University Medical Center GroningenGroningenthe Netherlands
- The Henry D. Janowitz Division of Gastroenterology, Department of MedicineIcahn School of Medicine at Mount Sinai, NYNew YorkNYUSA
| | - Martin F. Bourgonje
- Department of Pathology and Medical BiologyUniversity of Groningen, University Medical Center GroningenGroningenthe Netherlands
| | - Sacha la Bastide‐van Gemert
- Department of EpidemiologyUniversity of Groningen, University Medical Center GroningenGroningenthe Netherlands
| | | | | | - Ron T. Gansevoort
- Division of Nephrology, Department of Internal MedicineUniversity of Groningen, University Medical Center GroningenGroningenthe Netherlands
| | - Stephan J. L. Bakker
- Division of Nephrology, Department of Internal MedicineUniversity of Groningen, University Medical Center GroningenGroningenthe Netherlands
| | - Douwe J. Mulder
- Department of Internal Medicine, Division of Vascular MedicineUniversity of Groningen, University Medical Center GroningenGroningenthe Netherlands
| | - Robin P. F. Dullaart
- Department of Internal Medicine, Division of EndocrinologyUniversity of Groningen, University Medical Center GroningenGroningenthe Netherlands
| | - Amaal E. Abdulle
- Department of Internal Medicine, Division of Vascular MedicineUniversity of Groningen, University Medical Center GroningenGroningenthe Netherlands
| | - Harry van Goor
- Department of Pathology and Medical BiologyUniversity of Groningen, University Medical Center GroningenGroningenthe Netherlands
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Deris Zayeri Z, Parsi A, Shahrabi S, Kargar M, Davari N, Saki N. Epigenetic and metabolic reprogramming in inflammatory bowel diseases: diagnostic and prognostic biomarkers in colorectal cancer. Cancer Cell Int 2023; 23:264. [PMID: 37936149 PMCID: PMC10631091 DOI: 10.1186/s12935-023-03117-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Accepted: 10/27/2023] [Indexed: 11/09/2023] Open
Abstract
BACKGROUND AND AIM "Inflammatory bowel disease" (IBD) is a chronic, relapsing inflammatory disease of the intestinal tract that typically begins at a young age and might transit to colorectal cancer (CRC). In this manuscript, we discussed the epigenetic and metabolic change to present a extensive view of IBDs transition to CRC. This study discusses the possible biomarkers for evaluating the condition of IBDs patients, especially before the transition to CRC. RESEARCH APPROACH We searched "PubMed" and "Google Scholar" using the keywords from 2000 to 2022. DISCUSSION In this manuscript, interesting titles associated with IBD and CRC are discussed to present a broad view regarding the epigenetic and metabolic reprogramming and the biomarkers. CONCLUSION Epigenetics can be the main reason in IBD transition to CRC, and Hypermethylation of several genes, such as VIM, OSM4, SEPT9, GATA4 and GATA5, NDRG4, BMP3, ITGA4 and plus hypomethylation of LINE1 can be used in IBD and CRC management. Epigenetic, metabolisms and microbiome-derived biomarkers, such as Linoleic acid and 12 hydroxy 8,10-octadecadienoic acid, Serum M2-pyruvate kinase and Six metabolic genes (NAT2, XDH, GPX3, AKR1C4, SPHK and ADCY5) expression are valuable biomarkers for early detection and transition to CRC condition. Some miRs, such as miR-31, miR-139-5p, miR -155, miR-17, miR-223, miR-370-3p, miR-31, miR -106a, miR -135b and miR-320 can be used as biomarkers to estimate IBD transition to CRC condition.
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Affiliation(s)
- Zeinab Deris Zayeri
- Golestan Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Abazar Parsi
- Alimentary Tract Research Center, Clinical Sciences Research Inistitute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Saeid Shahrabi
- Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Masoud Kargar
- Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Nader Davari
- Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Najmaldin Saki
- Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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11
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Mecklenburg J, Shein SA, Malmir M, Hovhannisyan AH, Weldon K, Zou Y, Lai Z, Jin YF, Ruparel S, Tumanov AV, Akopian AN. Transcriptional profiles of non-neuronal and immune cells in mouse trigeminal ganglia. FRONTIERS IN PAIN RESEARCH 2023; 4:1274811. [PMID: 38028432 PMCID: PMC10644122 DOI: 10.3389/fpain.2023.1274811] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 09/29/2023] [Indexed: 12/01/2023] Open
Abstract
Non-neuronal cells constitute 90%-95% of sensory ganglia. These cells, especially glial and immune cells, play critical roles in the modulation of sensory neurons. This study aimed to identify, profile, and summarize the types of trigeminal ganglion (TG) non-neuronal cells in naïve male mice using published and our own data generated by single-cell RNA sequencing, flow cytometry, and immunohistochemistry. TG has five types of non-neuronal cells, namely, glial, fibroblasts, smooth muscle, endothelial, and immune cells. There is an agreement among publications for glial, fibroblasts, smooth muscle, and endothelial cells. Based on gene profiles, glial cells were classified as myelinated and non-myelinated Schwann cells and satellite glial cells. Mpz has dominant expression in Schwann cells, and Fabp7 is specific for SCG. Two types of Col1a2+ fibroblasts located throughout TG were distinguished. TG smooth muscle and endothelial cells in the blood vessels were detected using well-defined markers. Our study reported three types of macrophages (Mph) and four types of neutrophils (Neu) in TG. Mph were located in the neuronal bodies and nerve fibers and were sub-grouped by unique transcriptomic profiles with Ccr2, Cx3cr1, and Iba1 as markers. A comparison of databases showed that type 1 Mph is similar to choroid plexus-low (CPlo) border-associated Mph (BAMs). Type 2 Mph has the highest prediction score with CPhi BAMs, while type 3 Mph is distinct. S100a8+ Neu were located in the dura surrounding TG and were sub-grouped by clustering and expressions of Csf3r, Ly6G, Ngp, Elane, and Mpo. Integrative analysis of published datasets indicated that Neu-1, Neu-2, and Neu-3 are similar to the brain Neu-1 group, while Neu-4 has a resemblance to the monocyte-derived cells. Overall, the generated and summarized datasets on non-neuronal TG cells showed a unique composition of myeloid cell types in TG and could provide essential and fundamental information for studies on cell plasticity, interactomic networks between neurons and non-neuronal cells, and function during a variety of pain conditions in the head and neck regions.
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Affiliation(s)
- Jennifer Mecklenburg
- Department of Endodontics, School of Dentistry, The University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, United States
| | - Sergey A. Shein
- Microbiology, Immunology & Molecular Genetics Departments, School of Medicine, UTHSCSA, San Antonio, TX, United States
| | - Mostafa Malmir
- Department of Electrical and Computer Engineering, the University of Texas at San Antonio, San Antonio, TX, United States
| | - Anahit H. Hovhannisyan
- Department of Endodontics, School of Dentistry, The University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, United States
| | - Korri Weldon
- Molecular Medicine, School of Medicine, UTHSCSA, San Antonio, TX, United States
| | - Yi Zou
- Molecular Medicine, School of Medicine, UTHSCSA, San Antonio, TX, United States
| | - Zhao Lai
- Molecular Medicine, School of Medicine, UTHSCSA, San Antonio, TX, United States
- Greehey Children’s Cancer Research Institute, UTHSCSA, San Antonio, TX, United States
| | - Yu-Fang Jin
- Department of Electrical and Computer Engineering, the University of Texas at San Antonio, San Antonio, TX, United States
| | - Shivani Ruparel
- Department of Endodontics, School of Dentistry, The University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, United States
| | - Alexei V. Tumanov
- Microbiology, Immunology & Molecular Genetics Departments, School of Medicine, UTHSCSA, San Antonio, TX, United States
| | - Armen N. Akopian
- Department of Endodontics, School of Dentistry, The University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, United States
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Zhang L, Li J. Unlocking the secrets: the power of methylation-based cfDNA detection of tissue damage in organ systems. Clin Epigenetics 2023; 15:168. [PMID: 37858233 PMCID: PMC10588141 DOI: 10.1186/s13148-023-01585-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 10/11/2023] [Indexed: 10/21/2023] Open
Abstract
BACKGROUND Detecting organ and tissue damage is essential for early diagnosis, treatment decisions, and monitoring disease progression. Methylation-based assays offer a promising approach, as DNA methylation patterns can change in response to tissue damage. These assays have potential applications in early detection, monitoring disease progression, evaluating treatment efficacy, and assessing organ viability for transplantation. cfDNA released into the bloodstream upon tissue or organ injury can serve as a biomarker for damage. The epigenetic state of cfDNA, including DNA methylation patterns, can provide insights into the extent of tissue and organ damage. CONTENT Firstly, this review highlights DNA methylation as an extensively studied epigenetic modification that plays a pivotal role in processes such as cell growth, differentiation, and disease development. It then presents a variety of highly precise 5-mC methylation detection techniques that serve as powerful tools for gaining profound insights into epigenetic alterations linked with tissue damage. Subsequently, the review delves into the mechanisms underlying DNA methylation changes in organ and tissue damage, encompassing inflammation, oxidative stress, and DNA damage repair mechanisms. Next, it addresses the current research status of cfDNA methylation in the detection of specific organ tissues and organ damage. Finally, it provides an overview of the multiple steps involved in identifying specific methylation markers associated with tissue and organ damage for clinical trials. This review will explore the mechanisms and current state of research on cfDNA methylation-based assay detecting organ and tissue damage, the underlying mechanisms, and potential applications in clinical practice.
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Affiliation(s)
- Lijing Zhang
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, No. 1 Dahua Road, Dongdan, Beijing, 100730, People's Republic of China
- Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing Hospital, Beijing, People's Republic of China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing, People's Republic of China
| | - Jinming Li
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, No. 1 Dahua Road, Dongdan, Beijing, 100730, People's Republic of China.
- Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing Hospital, Beijing, People's Republic of China.
- Beijing Engineering Research Center of Laboratory Medicine, Beijing, People's Republic of China.
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13
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Mecklenburg J, Shein SA, Hovhannisyan AH, Zou Y, Lai Z, Ruparel S, Tumanov AV, Akopian AN. Transcriptional Profiles of Non-neuronal and Immune Cells in Mouse Trigeminal Ganglia. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.08.18.553897. [PMID: 37645736 PMCID: PMC10462109 DOI: 10.1101/2023.08.18.553897] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/31/2023]
Abstract
Non-neuronal cells constitute 90-95% of sensory ganglia. These cells play critical roles in modulation of nociceptive signal transmissions by sensory neurons. Accordingly, the aim of this review-study was to identify, profile and summarize TG non-neuronal cell types in naïve male mice using published and our own data generated by single-cell RNA sequencing (scRNA-seq), flow cytometry (FC) and immunohistochemistry (IHC). TG contains 5 types of non-neuronal cells: glial, fibroblasts, smooth muscle, endothelial and immune cells. There is agreement among publications for glial, fibroblasts, smooth muscle and endothelial cells. Based on gene profiles, glial cells were classified as Schwann cells and satellite glial cells (SGC). Mpz had dominant expression in Schwann cells, and Fabp7 is specific for SCG. Two types of Col1a2 + fibroblasts located throughout TG were distinguished using gene profiles. TG smooth muscle and endothelial cells representing blood vessels were detected with well recognized markers. Our study split reported single TG immune cell group into 3 types of macrophages and 4 types of neutrophils. Macrophages were located among neuronal bodies and nerve fibers, and were sub-grouped by unique transcriptomic profiles and using Ccr2 , Cx3cr1 and Iba1 as markers. S100a8 + neutrophils were located in dura surrounding TG and were sub-grouped by clustering and expressions of Csf3r , Ly6G, Ngp, Elane and Mpo . Overall, generated and summarized here dataset on non-neuronal TG cells could provide essential and fundamental information for studies on cell plasticity, interactomic network between neurons and non-neuronal cells and function during variety of pain conditions in the head and neck region.
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14
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Yu ZQ, Bai XY, Ruan GC, Han W, Xu TM, Zhang MY, Wang BM, Zhang YJ, Guo MY, Yang H. Autoimmune pancreatitis associated with inflammatory bowel diseases: A retrospectively bidirectional case-control study in China. J Dig Dis 2023; 24:452-460. [PMID: 37503771 DOI: 10.1111/1751-2980.13209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 07/02/2023] [Accepted: 07/25/2023] [Indexed: 07/29/2023]
Abstract
OBJECTIVES Autoimmune pancreatitis (AIP) is a rare and enigmatic immune-mediated inflammatory disease. We aimed to investigate the prevalence, characteristics, and associated factors of AIP-inflammatory bowel disease (IBD) in China. METHODS A retrospective bidirectional case-control study was performed. The diagnoses of IBD and AIP were made based on the European Crohn's and Colitis Organization guidelines and the International Consensus Diagnostic Criteria. IBD controls were matched by age, sex, and IBD type at a ratio of 1:4, while AIP controls were matched by AIP types. RESULTS The age-standardized prevalence of AIP-IBD patients in the IBD and AIP population were 292.0 and 8151.93 per 100 000 population, respectively. IBD patients had a higher risk of AIP compared to non-IBD patients (odds ratio 8.4, 95% confidence interval 4.7-14.9, P < 0.0001), and AIP patients had a higher risk of developing IBD compared to the general population in China. The mean age at diagnosis of IBD and AIP was 34.83 years and 40.42 years. IBD was diagnosed before AIP in seven cases. The median total IBD and AIP duration was 43.5 months and 13.5 months. Use of mesalamine and tuberculosis were associated with AIP in IBD patients (P = 0.031). And fecal occult blood test was associated with IBD in AIP patients (P = 0.008). CONCLUSIONS Most AIP-IBD patients had ulcerative colitis and type 2 AIP. IBD patients are more likely to develop AIP compared to the general population, and vice versa. Use of mesalamine and tuberculosis infection were associated with AIP, and fecal occult blood test was associated with IBD.
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Affiliation(s)
- Zi Qing Yu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiao Yin Bai
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Ge Chong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Wei Han
- Department of Epidemiology and Biostatistics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Tian Ming Xu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Meng Yuan Zhang
- Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Bei Ming Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yu Jia Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Ming Yue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Paysal J, Oris C, Troin U, Limeri PN, Allard J, Tadrent M, Pereira B, Merlin E, Rochette E, Evrard B, Durif J, Sapin V, Pons M. Influence of Perinatal Factors on Blood Tryptase and Fecal Calprotectin Levels in Newborns. CHILDREN (BASEL, SWITZERLAND) 2023; 10:345. [PMID: 36832475 PMCID: PMC9954950 DOI: 10.3390/children10020345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/31/2023] [Accepted: 02/08/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND Blood tryptase and fecal calprotectin levels may serve as biomarkers of necrotizing enterocolitis. However, their interpretation may be hindered by the little-known effects of perinatal factors. The aim of this study was to compare the tryptase and calprotectin levels in newborns according to their term, trophicity, and sex. METHOD One hundred and fifty-seven premature newborns and 157 full-term newborns were included. Blood tryptase and fecal calprotectin were assayed. RESULTS Blood tryptase levels were higher in premature than in full-term newborns (6.4 vs. 5.2 µg/L; p < 0.001). In situations of antenatal use of corticosteroids (p = 0.007) and non-exclusive use of human milk (p = 0.02), these levels were also higher. However, in multiple linear regression analyses, only prematurity significantly influenced tryptase levels. Fecal calprotectin levels were extremely wide-ranging and were much higher in female than in male newborns (300.5 vs. 110.5 µg/g; p < 0.001). CONCLUSIONS The differences in tryptase levels according to term could be linked to early aggression of the still-immature digestive wall in premature newborns, in particular, by enteral feeding started early. The unexpected influence of sex on fecal calprotectin levels remains unexplained.
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Affiliation(s)
- Justine Paysal
- CHU Clermont-Ferrand, Néonatologie et Réanimation Pédiatrique, F-63000 Clermont-Ferrand, France
- INSERM, CIC 1405, CRECHE Unit, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France
| | - Charlotte Oris
- CHU Clermont-Ferrand Gabriel Montpied, Biochimie, F-63000 Clermont-Ferrand, France
| | - Ugo Troin
- INSERM, CIC 1405, CRECHE Unit, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France
| | - Pierre-Nicolas Limeri
- INSERM, CIC 1405, CRECHE Unit, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France
| | - Jeanne Allard
- INSERM, CIC 1405, CRECHE Unit, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France
| | - Marie Tadrent
- INSERM, CIC 1405, CRECHE Unit, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France
| | - Bruno Pereira
- CHU Clermont-Ferrand, Direction de la Recherche Clinique et de l’Innovation, Secteur Biométrie et Médico-économi, F-63000 Clermont-Ferrand, France
| | - Etienne Merlin
- INSERM, CIC 1405, CRECHE Unit, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France
- CHU Clermont-Ferrand, Pédiatrie, F-63000 Clermont-Ferrand, France
| | - Emmanuelle Rochette
- INSERM, CIC 1405, CRECHE Unit, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France
- CHU Clermont-Ferrand, Pédiatrie, F-63000 Clermont-Ferrand, France
| | - Bertrand Evrard
- CHU Clermont-Ferrand, Immunologie, F-63000 Clermont-Ferrand, France
| | - Julie Durif
- CHU Clermont-Ferrand Gabriel Montpied, Biochimie, F-63000 Clermont-Ferrand, France
| | - Vincent Sapin
- CHU Clermont-Ferrand Gabriel Montpied, Biochimie, F-63000 Clermont-Ferrand, France
| | - Maguelonne Pons
- CHU Clermont-Ferrand, Chirurgie Pédiatrique, F-63000 Clermont-Ferrand, France
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Feysa SV, Pushkarenko OA, Rudakova SO, Varvarynets AV. IS FECAL CALPROTECTIN DETERMINATION USEFUL FOR PATIENTS WITH METABOLIC ASSOCIATED FATTY LIVER DISEASE? POLSKI MERKURIUSZ LEKARSKI : ORGAN POLSKIEGO TOWARZYSTWA LEKARSKIEGO 2023; 51:330-333. [PMID: 37756451 DOI: 10.36740/merkur202304105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/29/2023]
Abstract
OBJECTIVE Aim: To investigate the possible relationship between fecal calprotectin (FC) level and ultrasound indicators of steatosis and fibrosis wich defined by attenuation coefficient (AC) and liver stiffness (LS) from two-dimensional (2D) shear-wave elastography (SWE) in patients with metabolically associated fatty liver disease (MAFLD). PATIENTS AND METHODS Materials and Methods: The study included 110 persons with MAFLD; mean age 51.3±4.8 years, 65 (59.1%) men. There were used laboratory, sonography and statistical methods. RESULTS Results: Stage S1 of steatosis was diagnosed in 42 (38.2%), S2 - in 56 (50.9%), S3 - only in 12 (10.9%) MAFLD patients. The carbohydrate metabolism disorders were found in 62 (56.4%); 38 (34.5%) patients among them suffered from type 2 diabetes. The lipid metabolism disorders were diagnosed in the vast majority of patients included in this study. The minimal excess of fecal calprotectin (FC) was detected in 72 MAFLD patients (65.5%), the moderate increase of FC was found in 12 persons, the FC more than 10-fold excess of the norm was observed in only 8 MAFLD patients. FC levels were significantly elevated in MAFLD patients with a S2-S3 compared to those with a S1 (75.8 [42.9-112.1] vs. 46.3 [28.2-65.4], p<0.01). CONCLUSION Conclusions: Fecal calprotectin levels are significantly elevated in patients with MAFLD. Future studies are warranted to establish the definitive role and clinical utility of FC as a potential biomarker of probably liver steatosis as well as other diseases associated with methabolic syndrome and its complications.
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Affiliation(s)
- Snizhana V Feysa
- STATE HIGHER EDUCATIONAL ESTABLISHMENT "UZHHOROD NATIONAL UNIVERSITY", UZHHOROD, UKRAINE
| | - Olga A Pushkarenko
- STATE HIGHER EDUCATIONAL ESTABLISHMENT "UZHHOROD NATIONAL UNIVERSITY", UZHHOROD, UKRAINE
| | - Svitlana O Rudakova
- STATE HIGHER EDUCATIONAL ESTABLISHMENT "UZHHOROD NATIONAL UNIVERSITY", UZHHOROD, UKRAINE
| | - Antonina V Varvarynets
- STATE HIGHER EDUCATIONAL ESTABLISHMENT "UZHHOROD NATIONAL UNIVERSITY", UZHHOROD, UKRAINE
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Plasma Calprotectin Levels Associate with Suspected Metabolic-Associated Fatty Liver Disease and All-Cause Mortality in the General Population. Int J Mol Sci 2022; 23:ijms232415708. [PMID: 36555350 PMCID: PMC9778771 DOI: 10.3390/ijms232415708] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/07/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) is characterized by hepatic steatosis, metabolic dysregulation, and neutrophilic inflammation. In this study, we hypothesized that systemic levels of plasma calprotectin, as a biomarker of neutrophilic inflammation, may be associated with suspected MAFLD. Plasma calprotectin levels were measured in subjects (n = 5446) participating in the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort study. Suspected MAFLD was defined by the fatty liver index (FLI ≥ 60) and hepatic steatosis index (HSI ≥ 36) as proxies. Plasma calprotectin levels were significantly higher in subjects with FLI ≥ 60 (0.57 [IQR: 0.42−0.79] mg/L, n = 1592) (p < 0.001) compared to subjects with FLI < 60 (0.46 [0.34−0.65] mg/L, n = 3854). Multivariable logistic regression analyses revealed that plasma calprotectin levels were significantly associated with suspected MAFLD (FLI ≥ 60), even after adjustment for potential confounding factors, including current smoking, alcohol consumption, hypertension, diabetes, cardiovascular diseases, insulin resistance (HOMA-IR), hs-CRP, eGFR, and total cholesterol levels (OR 1.19 [95% CI: 1.06−1.33], p = 0.003). Interaction analyses revealed significant effect modifications for the association between plasma calprotectin and suspected MAFLD by BMI (p < 0.001) and hypertension (p = 0.003), with the strongest associations in subjects with normal BMI and without hypertension. Prospectively, plasma calprotectin levels were significantly associated with all-cause mortality after adjustment for potential confounding factors, particularly in subjects without suspected MAFLD (FLI < 60) (hazard ratio (HR) per doubling: 1.34 (1.05−1.72), p < 0.05). In conclusion, higher plasma calprotectin levels are associated with suspected MAFLD and with the risk of all-cause mortality, the latter especially in subjects without suspected MAFLD.
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Romero-Mascarell C, Fernández-Esparrach G, Rodríguez-De Miguel C, Masamunt MC, Rodríguez S, Rimola J, Urpí M, Casanova GS, Ordás I, Ricart E, Caballol B, Fernández-Clotet A, Panés J, Llach J, González-Suárez B. Fecal Calprotectin for Small Bowel Crohn's Disease: Is It a Cutoff Issue? Diagnostics (Basel) 2022; 12:diagnostics12092226. [PMID: 36140627 PMCID: PMC9497577 DOI: 10.3390/diagnostics12092226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/03/2022] [Accepted: 09/05/2022] [Indexed: 11/16/2022] Open
Abstract
(1) Background: Fecal calprotectin (FC) correlates well with colonic inflammatory activity of Crohn’s disease (CD); data about relation of FC and small bowel (SB) lesions are still contradictory. The main aim was to analyze the relationship between FC levels and SB inflammatory activity in patients with established or suspected Crohn’s disease, assessed by small bowel capsule endoscopy (SBCE) or magnetic resonance enterography (MRE). (2) Methods: Two cohorts of patients were included: 1. Prospective data were collected from patients with established or suspected CD who underwent SBCE and FC (Cohort A); 2. A retrospective cohort of patients who underwent MRE and FC determination (Cohort B). Different cutoffs for FC were tested in both cohorts. (3) Results: 83 patients were included and 66 were finally analyzed. A total of 69.6% had SB lesions seen by SBCE (n = 25) or MRE (n = 21). FC mean levels were 605.74 + 607.07 μg/g (IQ range: 99.00−878.75), being significantly higher in patients with SB lesions compared to patients without lesions (735.91 + 639.70 μg/g (IQ range: 107.75−1366.25) vs. 306.35 + 395.26 μg/g (IQ range: 78.25−411.0), p < 0.005). For cohort A, 25 out of 35 patients had SB lesions and a significant correlation between Lewis Score and FC levels was achieved (R2: 0.34; p = 0.04). FC sensitivity (S), specificity (E), positive predictive value (PPV), and negative predictive values (NPV) for predicting SB lesions were 80%, 50%, 80%, and 50%, respectively, for FC > 100 µg/g. For cohort B, inflammatory SB activity, measured by MaRIA score, was detected in 21 out of 31 patients (67.7%). Patients with positive findings in MRE had significantly higher values of FC than those with no lesions (944.9 + 672.1 µg/g vs. 221 + 212.2 µg/g, p < 0.05). S, E, PPV, and NPV of FC were 89%, 50%, 77.2%, and 71.4% for FC levels > 100 µg/g. The higher sensitivity and specificity of the FC levels for the detection of SB lesions with SBCE and MRE was obtained for an FC cutoff >265 μg/g and >430 μg/g, respectively. (4) Conclusions: FC has a good correlation with the presence of SB lesions, assessed by SBCE and MRE, in patients with established or suspected Crohn’s disease. However, the ideal cutoff is here proven to be higher than previously reported. Multicenter and large prospective studies are needed in order to establish definitive FC cutoff levels.
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Affiliation(s)
- Cristina Romero-Mascarell
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Gloria Fernández-Esparrach
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
| | - Cristina Rodríguez-De Miguel
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Maria Carme Masamunt
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Sonia Rodríguez
- Department of Radiology, Centre de Diagnòstic per la Imatge (CDI), Hospital Clínic Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Jordi Rimola
- Department of Radiology, Centre de Diagnòstic per la Imatge (CDI), Hospital Clínic Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Miguel Urpí
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Gherzon Simon Casanova
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Ingrid Ordás
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Elena Ricart
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Berta Caballol
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Agnès Fernández-Clotet
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Julià Panés
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Josep Llach
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
| | - Begoña González-Suárez
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Correspondence:
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19
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Randrianarisoa MM, Rakotondrainipiana M, Randriamparany R, Andriantsalama PV, Randrianarijaona A, Habib A, Robinson A, Raharimalala L, Hunald FA, Etienne A, Collard JM, Randrianirina F, Barouki R, Pontoizeau C, Nestoret A, Kapel N, Sansonetti P, Vonaesch P, Randremanana RV. Factors associated with anaemia among preschool- age children in underprivileged neighbourhoods in Antananarivo, Madagascar. BMC Public Health 2022; 22:1320. [PMID: 35810292 PMCID: PMC9271242 DOI: 10.1186/s12889-022-13716-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 06/07/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Anaemia occurs in children when the haemoglobin level in the blood is less than the normal (11 g/dL), the consequence is the decrease of oxygen quantity in the tissues. It is a prevalent public health problem in many low-income countries, including Madagascar, and data on risk factors are lacking. We used existing data collected within the pathophysiology of environmental enteric dysfunction (EED) in Madagascar and the Central African Republic project (AFRIBIOTA project) conducted in underprivileged neighbourhoods of Antananarivo to investigate the factors associated with anaemia in children 24 to 59 months of age. METHODS Children included in the AFRIBIOTA project in Antananarivo for whom data on haemoglobin and ferritin concentrations were available were included in the study. Logistic regression modelling was performed to identify factors associated with anaemia. RESULTS Of the 414 children included in this data analysis, 24.4% were found to suffer from anaemia. We found that older children (adjusted OR: 0.95; 95% CI: 0.93-0.98) were less likely to have anaemia. Those with iron deficiency (adjusted OR: 6.1; 95% CI: 3.4-11.1) and those with a high level of faecal calprotectin (adjusted OR: 2.5; 95% CI: 1.4-4.4) were more likely to have anaemia than controls. CONCLUSIONS To reduce anaemia in the children in this underprivileged area, more emphasis should be given to national strategies that improve children's dietary quality and micronutrient intake. Furthermore, existing measures should be broadened to include measures to reduce infectious disease burden.
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Affiliation(s)
- Mirella Malala Randrianarisoa
- Institut Pasteur de Madagascar, Unité Epidémiologie et de Recherche Clinique, BP 1274, Ambatofotsikely, 101, Antananarivo, Madagascar
| | - Maheninasy Rakotondrainipiana
- Institut Pasteur de Madagascar, Unité Epidémiologie et de Recherche Clinique, BP 1274, Ambatofotsikely, 101, Antananarivo, Madagascar
| | - Ravaka Randriamparany
- Institut Pasteur de Madagascar, Unité Epidémiologie et de Recherche Clinique, BP 1274, Ambatofotsikely, 101, Antananarivo, Madagascar
| | - Prisca Vega Andriantsalama
- Institut Pasteur de Madagascar, Unité Epidémiologie et de Recherche Clinique, BP 1274, Ambatofotsikely, 101, Antananarivo, Madagascar
| | - Anjasoa Randrianarijaona
- Institut Pasteur de Madagascar, Unité Epidémiologie et de Recherche Clinique, BP 1274, Ambatofotsikely, 101, Antananarivo, Madagascar
| | - Azimdine Habib
- Institut Pasteur de Madagascar, Unité Epidémiologie et de Recherche Clinique, BP 1274, Ambatofotsikely, 101, Antananarivo, Madagascar
| | - Annick Robinson
- Centre Hospitalier Universitaire Mère Enfant de Tsaralalana, rue Patrice Lumumba, Rue Mabizo S, 101, Antananarivo, Madagascar
| | - Lisette Raharimalala
- Centre de Santé Maternelle et Infantile de Tsaralalana, Lalana Andriantsilavo, 101, Antananarivo, Madagascar
| | - Francis Allen Hunald
- Service de Chirurgie pédiatrique, Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona, BP 4150, Ampefiloha, 101, Antananarivo, Madagascar
| | - Aurélie Etienne
- Institut Pasteur de Madagascar, Unité Epidémiologie et de Recherche Clinique, BP 1274, Ambatofotsikely, 101, Antananarivo, Madagascar
| | - Jean-Marc Collard
- Institut Pasteur de Madagascar, Unité Epidémiologie et de Recherche Clinique, BP 1274, Ambatofotsikely, 101, Antananarivo, Madagascar.,The Center for Microbes, Development and Health, Institut Pasteur of Shanghai/Chinese Academy of Sciences, Shanghai, China
| | - Frédérique Randrianirina
- Institut Pasteur de Madagascar, Unité Epidémiologie et de Recherche Clinique, BP 1274, Ambatofotsikely, 101, Antananarivo, Madagascar
| | - Robert Barouki
- Laboratoire de Biochimie Métabolomique et Protéomique, Hôpital Universitaire Necker-Enfants Malades, Paris, France
| | - Clement Pontoizeau
- Laboratoire de Biochimie Métabolomique et Protéomique, Hôpital Universitaire Necker-Enfants Malades, Paris, France
| | - Alison Nestoret
- Service de Coprologie Fonctionnelle, Hôpital Salpétrière Paris, Paris, France
| | - Nathalie Kapel
- Service de Coprologie Fonctionnelle, Hôpital Salpétrière Paris, Paris, France
| | - Philippe Sansonetti
- Unité de Pathogénie Microbienne, Institut Pasteur, 25-28 Rue du Dr Roux, Paris, France
| | - Pascale Vonaesch
- Unité de Pathogénie Microbienne, Institut Pasteur, 25-28 Rue du Dr Roux, Paris, France.,Department of Fundamental Microbiology, University of Lausanne, Campus UNIL-Sorge, 1015, Lausanne, Switzerland
| | - Rindra Vatosoa Randremanana
- Institut Pasteur de Madagascar, Unité Epidémiologie et de Recherche Clinique, BP 1274, Ambatofotsikely, 101, Antananarivo, Madagascar.
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Nooredinvand HA, Poullis A. Emerging role of colorectal mucus in gastroenterology diagnostics. World J Gastroenterol 2022; 28:1220-1225. [PMID: 35431508 PMCID: PMC8968490 DOI: 10.3748/wjg.v28.i12.1220] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 07/29/2021] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
Colonoscopy is currently the gold standard for diagnosis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). This has the obvious drawback of being invasive as well as carrying a small risk. The most widely used non-invasive approaches include the use of faecal calprotectin in the case of IBD and fecal immunochemical test in the case of CRC. However, the necessity of stool collection limits their acceptability for some patients. Over the recent years, there has been emerging data looking at the role of non-invasively obtained colorectal mucus as a screening and diagnostic tool in IBD and CRC. It has been shown that the mucus rich material obtained by self-sampling of anal surface following defecation, can be used to measure various biomarkers that can aid in diagnosis of these conditions.
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Affiliation(s)
| | - Andrew Poullis
- Department of Gastroenterology, St George's Hospital, London SW17 0QT, United Kingdom
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21
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Ruan J, Schlüter D, Naumann M, Waisman A, Wang X. Ubiquitin-modifying enzymes as regulators of colitis. Trends Mol Med 2022; 28:304-318. [PMID: 35177326 DOI: 10.1016/j.molmed.2022.01.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 01/24/2022] [Accepted: 01/24/2022] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract. Although the pathophysiology of IBD is multifaceted, ubiquitination, a post-translational modification, has been shown to have essential roles in its pathogenesis and development. Ubiquitin-modifying enzymes (UMEs) work in synergy to orchestrate the optimal ubiquitination of target proteins, thereby maintaining intestinal homeostasis. Genome-wide association studies (GWAS) have identified multiple UME genes as IBD susceptibility loci, implying the importance of UMEs in IBD. Furthermore, accumulative evidence demonstrates that UMEs affect intestinal inflammation by regulating various aspects, such as intestinal barrier functions and immune responses. Considering the significant functions of UMEs in IBD, targeting UMEs could become a favorable therapeutic approach for IBD.
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Affiliation(s)
- Jing Ruan
- Department of Pathology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Dirk Schlüter
- Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Michael Naumann
- Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Ari Waisman
- Institute for Molecular Medicine, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Xu Wang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, China; Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
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22
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Hadji H, Bouchemal K. Advances in the treatment of inflammatory bowel disease: Focus on polysaccharide nanoparticulate drug delivery systems. Adv Drug Deliv Rev 2022; 181:114101. [PMID: 34999122 DOI: 10.1016/j.addr.2021.114101] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 12/21/2021] [Accepted: 12/22/2021] [Indexed: 02/07/2023]
Abstract
The complex pathogenesis of inflammatory bowel disease (IBD) explains the several hurdles for finding an efficient approach to cure it. Nowadays, therapeutic protocols aim to reduce inflammation during the hot phase or maintain remission during the cold phase. Nonetheless, these drugs suffer from severe side effects or poor efficacy due to low bioavailability in the inflamed region of the intestinal tract. New protocols based on antibodies that target proinflammatory cytokines are clinically relevant. However, besides being expensive, their use is associated with a primary nonresponse or a loss of response following a long administration period. Accordingly, many researchers exploited the physiological changes of the mucosal barrier for designing nanoparticulate drug delivery systems to target inflamed tissues. Others exploited biocompatibility and relative affordability of polysaccharides to test their intrinsic anti-inflammatory and healing properties in IBD models. This critical review updates state of the art on advances in IBD treatment. Data on using polysaccharide nanoparticulate drug delivery systems for IBD treatment are reviewed and discussed.
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Affiliation(s)
- Hicheme Hadji
- Institut Galien Paris Saclay, CNRS UMR 8612, Université Paris-Saclay, Faculté de Pharmacie, 5 rue J-B Clément, 92296 Châtenay-Malabry, France
| | - Kawthar Bouchemal
- Institut Galien Paris Saclay, CNRS UMR 8612, Université Paris-Saclay, Faculté de Pharmacie, 5 rue J-B Clément, 92296 Châtenay-Malabry, France.
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23
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Talley S, Valiauga R, Anderson L, Cannon AR, Choudhry MA, Campbell EM. DSS-induced inflammation in the colon drives a proinflammatory signature in the brain that is ameliorated by prophylactic treatment with the S100A9 inhibitor paquinimod. J Neuroinflammation 2021; 18:263. [PMID: 34758843 PMCID: PMC8578918 DOI: 10.1186/s12974-021-02317-6] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 11/03/2021] [Indexed: 12/23/2022] Open
Abstract
Background Inflammatory bowel disease (IBD) is established to drive pathological sequelae in organ systems outside the intestine, including the central nervous system (CNS). Many patients exhibit cognitive deficits, particularly during disease flare. The connection between colonic inflammation and neuroinflammation remains unclear and characterization of the neuroinflammatory phenotype in the brain during colitis is ill-defined. Methods Transgenic mice expressing a bioluminescent reporter of active caspase-1 were treated with 2% dextran sodium sulfate (DSS) for 7 days to induce acute colitis, and colonic, systemic and neuroinflammation were assessed. In some experiments, mice were prophylactically treated with paquinimod (ABR-215757) to inhibit S100A9 inflammatory signaling. As a positive control for peripheral-induced neuroinflammation, mice were injected with lipopolysaccharide (LPS). Colonic, systemic and brain inflammatory cytokines and chemokines were measured by cytokine bead array (CBA) and Proteome profiler mouse cytokine array. Bioluminescence was quantified in the brain and caspase activation was confirmed by immunoblot. Immune cell infiltration into the CNS was measured by flow cytometry, while light sheet microscopy was used to monitor changes in resident microglia localization in intact brains during DSS or LPS-induced neuroinflammation. RNA sequencing was performed to identify transcriptomic changes occurring in the CNS of DSS-treated mice. Expression of inflammatory biomarkers were quantified in the brain and serum by qRT-PCR, ELISA and WB. Results DSS-treated mice exhibited clinical hallmarks of colitis, including weight loss, colonic shortening and inflammation in the colon. We also detected a significant increase in inflammatory cytokines in the serum and brain, as well as caspase and microglia activation in the brain of mice with ongoing colitis. RNA sequencing of brains isolated from DSS-treated mice revealed differential expression of genes involved in the regulation of inflammatory responses. This inflammatory phenotype was similar to the signature detected in LPS-treated mice, albeit less robust and transient, as inflammatory gene expression returned to baseline following cessation of DSS. Pharmacological inhibition of S100A9, one of the transcripts identified by RNA sequencing, attenuated colitis severity and systemic and neuroinflammation. Conclusions Our findings suggest that local inflammation in the colon drives systemic inflammation and neuroinflammation, and this can be ameliorated by inhibition of the S100 alarmin, S100A9. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-021-02317-6.
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Affiliation(s)
- Sarah Talley
- Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL, USA
| | - Rasa Valiauga
- Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
| | - Lillian Anderson
- Alcohol Research Program, Burn and Shock Trauma Research Institute, Stritch School of Medicine, Loyola University Chicago Health Science Division, Maywood, IL, USA
| | - Abigail R Cannon
- Alcohol Research Program, Burn and Shock Trauma Research Institute, Stritch School of Medicine, Loyola University Chicago Health Science Division, Maywood, IL, USA
| | - Mashkoor A Choudhry
- Alcohol Research Program, Burn and Shock Trauma Research Institute, Stritch School of Medicine, Loyola University Chicago Health Science Division, Maywood, IL, USA
| | - Edward M Campbell
- Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL, USA. .,Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
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24
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Vakili M, Fahimi D, Esfahani ST, Sharifzadeh M, Moghtaderi M. Comparative Analysis between Urinary Calprotectin and Serum Creatinine for Early Detection of Intrinsic Acute Kidney Injury. Indian J Nephrol 2021; 31:353-357. [PMID: 34584350 PMCID: PMC8443099 DOI: 10.4103/ijn.ijn_83_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 08/16/2020] [Accepted: 08/20/2020] [Indexed: 12/14/2022] Open
Abstract
Background Acute kidney injury (AKI) is a common and important clinical condition that may lead to chronic kidney disease if it is not diagnosed and treated in its early stages. Urinary calprotectin is a valuable recognized biomarker that can be used to differentiate prerenal and intrinsic AKI. However, till date only a few reports on urine calprotectin measurement in early diagnosis of intrinsic AKI are available. In this study, we compared the sensitivity and specificity of urinary calprotectin with those of serum creatinine in detecting early intrinsic AKI. Methods Over 6 months period (April to October 2018), 81 of 408 patients admitted to the pediatric intensive care unit met the criteria of this cross-sectional study. Their serum creatinine and urinary calprotectin were measured on the first and third day of admission using Jaffe and Elisa radioimmunoassay methods, respectively. The AKI was defined according to the pRIFLE criteria. Results Of the total 81 patients, 67 had the criteria of intrinsic AKI. Of these 62% were female and 38% were male. The mean age of the patients was 22 months. According to data analysis, the area under the curve of ROC of urinary calprotectin on day-1 to detect renal failure is 0.93 with the best cutoff point obtained at 530 ng/mL. The sensitivity, specificity, positive, and negative predictive values of urinary calprotectin levels in diagnosing AKI at this cutoff point are 92.5%, 92.8%, 98.4, and 72.2%, respectively. Besides, urinary calprotectin changes occur much earlier than the rising of serum creatinine. Conclusion Urinary level of calprotectin is a very sensitive biomarker for early diagnosis of intrinsic AKI in children and it can be used in intensive care units or anywhere critically ill children admitted to detect intrinsic AKI. Besides, this study shows that urine calprotectin may be a more sensitive and specific biomarker than serum creatinine in the early phases of intrinsic AKI.
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Affiliation(s)
- Marjan Vakili
- Pediatric Nephrologist, Department of Pediatric Nephrology, Imam Ali Hospital, Alborz University of Medical Sciences, Karaj, Iran
| | - Daryoush Fahimi
- Associated Professor of Pediatric Nephrology, Pediatric Chronic Kidney Diseases Research Center, Pediatric Center of Excellence, Tehran University of Medical Science, Tehran, Iran
| | - Seyed-Taher Esfahani
- Professor of Pediatric Nephrology, Pediatric Center of Excellence, Tehran University of Medical Science, Tehran, Iran
| | - Meysam Sharifzadeh
- Fellowship of NICU, Children Medical Center Hospital, Tehran University of Medical Science, Tehran, Iran
| | - Mastaneh Moghtaderi
- Associated Professor of Pediatric Nephrology, Pediatric Chronic Kidney Disease Research Center, Pediatric Center of Excellence, Tehran University of Medical Science, Tehran, Iran
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25
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Ciregia F, Nys G, Cobraiville G, Badot V, Di Romana S, Sidiras P, Sokolova T, Durez P, Fillet M, Malaise MG, de Seny D. A Cross-Sectional and Longitudinal Study to Define Alarmins and A-SAA Variants as Companion Markers in Early Rheumatoid Arthritis. Front Immunol 2021; 12:638814. [PMID: 34489924 PMCID: PMC8418532 DOI: 10.3389/fimmu.2021.638814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 08/04/2021] [Indexed: 11/24/2022] Open
Abstract
Nowadays, in the study of rheumatoid arthritis (RA), more and more interest is directed towards an earlier effective therapeutic intervention and the determination of companion markers for predicting response to therapy with the goal to prevent progressive joint damage, deformities, and functional disability. With the present work, we aimed at quantifying in a cohort of early RA (ERA) patients naïve to DMARD therapy, proteins whose increase was previously found associated with RA: serum amyloid A (A-SAA) and alarmins. Five A-SAA variants (SAA1α, SAA1β, SAA1γ, SAA2α, and SAA2β) but also S100A8 and S100A9 proteins were simultaneously quantified in plasma applying a method based on single targeted bottom-up proteomics LC-MS/MS. First, we compared their expression between ERA (n = 100) and healthy subjects (n = 100), then we focused on their trend by monitoring ERA patients naïve to DMARD treatment, 1 year after starting therapy. Only SAA1α and SAA2α levels were increased in ERA patients, and SAA2α appears to mostly mediate the pathological role of A-SAA. Levels of these variants, together with SAA1β, only decreased under biologic DMARD treatment but not under methotrexate monotherapy. This study highlights the importance to better understand the modulation of expression of these variants in ERA in order to subsequently better characterize their biological function. On the other hand, alarmin expression increased in ERA compared to controls but remained elevated after 12 months of methotrexate or biologic treatment. The work overcomes the concept of considering these proteins as biomarkers for diagnosis, demonstrating that SAA1α, SAA1β, and SAA2α variants but also S100A8 and S100A9 do not respond to all early treatment in ERA and should be rather considered as companion markers useful to improve the follow-up of treatment response and remission state. Moreover, it suggests that earlier use of biologics in addition to methotrexate may be worth considering.
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Affiliation(s)
- Federica Ciregia
- Laboratory of Rheumatology, University of Liège, Centre Hospitalier Universitaire (CHU) de Liège, Liège, Belgium
| | - Gwenaël Nys
- Laboratory for the Analysis of Medicines, Centre Interdisciplinaire De Recherche Sur Le Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium
| | - Gaël Cobraiville
- Laboratory of Rheumatology, University of Liège, Centre Hospitalier Universitaire (CHU) de Liège, Liège, Belgium
| | - Valérie Badot
- Department of Rheumatology, Centre Hospitalier Universitaire (CHU) Brugmann, Bruxelles, Belgium
| | - Silvana Di Romana
- Department of Rheumatology, Centre Hospitalier Universitaire (CHU) Saint–Pierre, Bruxelles, Belgium
| | - Paschalis Sidiras
- Department of Rheumatology, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Tatiana Sokolova
- Department of Rheumatology, Cliniques Universitaires Saint–Luc, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Bruxelles, Belgium
| | - Patrick Durez
- Department of Rheumatology, Cliniques Universitaires Saint–Luc, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Bruxelles, Belgium
| | - Marianne Fillet
- Laboratory for the Analysis of Medicines, Centre Interdisciplinaire De Recherche Sur Le Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium
| | - Michel G. Malaise
- Laboratory of Rheumatology, University of Liège, Centre Hospitalier Universitaire (CHU) de Liège, Liège, Belgium
| | - Dominique de Seny
- Laboratory of Rheumatology, University of Liège, Centre Hospitalier Universitaire (CHU) de Liège, Liège, Belgium
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26
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Febo E, Crisi PE, Oddi S, Pietra M, Galiazzo G, Piscitelli F, Gramenzi A, Prinzio RD, Di Tommaso M, Bernabò N, Bisogno T, Maccarrone M, Boari A. Circulating Endocannabinoids as Diagnostic Markers of Canine Chronic Enteropathies: A Pilot Study. Front Vet Sci 2021; 8:655311. [PMID: 34124221 PMCID: PMC8187750 DOI: 10.3389/fvets.2021.655311] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 05/04/2021] [Indexed: 12/11/2022] Open
Abstract
Chronic enteropathies (CEs) in dogs, according to the treatment response to consecutive trials, are classified as food-responsive (FRE), antibiotic-responsive (ARE), and immunosuppressive-responsive (IRE) enteropathy. In addition to this classification, dogs with loss of protein across the gut are grouped as protein-losing enteropathy (PLE). At present, the diagnosis of CEs is time-consuming, costly and sometimes invasive, also because non-invasive biomarkers with high sensitivity and specificity are not yet available. Therefore, this study aimed at assessing the levels of circulating endocannabinoids in plasma as potential diagnostic markers of canine CEs. Thirty-three dogs with primary chronic gastrointestinal signs presented to Veterinary Teaching Hospitals of Teramo and Bologna (Italy) were prospectively enrolled in the study, and 30 healthy dogs were included as a control group. Plasma levels of N-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA) were measured at the time of the first visit in dogs with different CEs, as well as in healthy subjects. Plasma levels of 2-AG (p = 0.001) and PEA (p = 0.008) were increased in canine CEs compared to healthy dogs. In particular, PEA levels were increased in the FRE group compared to healthy dogs (p = 0.04), while 2-AG was higher in IRE than in healthy dogs (p = 0.0001). Dogs affected by FRE also showed decreased 2-AG (p = 0.0001) and increased OEA levels (p = 0.0018) compared to IRE dogs. Moreover, dogs with PLE showed increased 2-AG (p = 0.033) and decreased AEA (p = 0.035), OEA (p = 0.016) and PEA (p = 0.023) levels, when compared to dogs affected by CEs without loss of proteins. The areas under ROC curves for circulating 2-AG (0.91; 95% confidence interval [CI], 0.79–1.03) and OEA (0.81; 95% CI, 0.65–0.97) showed a good accuracy in distinguishing the different forms of CEs under study (FRE, ARE and IRE), at the time of the first visit. The present study demonstrated that endocannabinoid signaling is altered in canine CEs, and that CE subtypes showed distinct profiles of 2-AG, PEA and OEA plasma levels, suggesting that these circulating bioactive lipids might have the potential to become candidate biomarkers for canine CEs.
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Affiliation(s)
- Elettra Febo
- Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy
| | | | - Sergio Oddi
- Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.,European Center for Brain Research/Santa Lucia Foundation Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
| | - Marco Pietra
- Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Giorgia Galiazzo
- Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Fabiana Piscitelli
- Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Italy
| | | | | | | | - Nicola Bernabò
- Faculty of Bioscience, and Technology for Food Agriculture and Environment, University of Teramo, Teramo, Italy.,Institute of Biochemistry and Cell Biology, National Research Council, Rome, Italy
| | - Tiziana Bisogno
- Institute of Translational Pharmacology, National Research Council, Rome, Italy
| | - Mauro Maccarrone
- European Center for Brain Research/Santa Lucia Foundation Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.,Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Andrea Boari
- Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy
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27
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Yusuf F, Fahriani M, Mamada SS, Frediansyah A, Abubakar A, Maghfirah D, Fajar JK, Maliga HA, Ilmawan M, Emran TB, Ophinni Y, Innayah MR, Masyeni S, Ghouth ASB, Yusuf H, Dhama K, Nainu F, Harapan H. Global prevalence of prolonged gastrointestinal symptoms in COVID-19 survivors and potential pathogenesis: A systematic review and meta-analysis. F1000Res 2021; 10:301. [PMID: 34131481 PMCID: PMC8171196 DOI: 10.12688/f1000research.52216.1] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/09/2021] [Indexed: 12/13/2022] Open
Abstract
Background: This study aimed to determine the cumulative prevalence of prolonged gastrointestinal (GI) symptoms, including nausea, vomiting, diarrhea, lack of appetite, abdominal pain, and dysgeusia, in survivors of both mild and severe COVID-19 worldwide and to discuss the potential pathogenesis. Methods: Three databases (PubMed, Scopus, and Web of Science) were searched for relevant articles up to January 30, 2021. Data on study characteristics, clinical characteristics during follow-up, the number of patients with prolonged GI symptoms, and total number of COVID-19 survivors were retrieved according to PRISMA guidelines. The quality of eligible studies was assessed using the Newcastle-Ottawa scale. The pooled prevalence of specific prolonged GI symptoms was calculated and the association between COVID-19 severity and the occurrence of prolonged GI symptoms was assessed if appropriate. Results: The global prevalence of prolonged nausea was 3.23% (95% CI: 0.54%-16.53%) among 527 COVID-19 survivors. Vomiting persisted in 93 of 2,238 COVID-19 survivors (3.19%, 95% CI: 1.62%-6.17%) and prolonged diarrhea was found in 34 of 1,073 survivors (4.12%, 95% CI: 1.07%-14.64%). A total of 156 patients among 2,238 COVID-19 survivors (4.41%, 95% CI: 1.91%-9.94%) complained of persistent decreased or loss of appetite. The cumulative prevalence of prolonged abdominal pain was 1.68% (95% CI: 0.84%-3.32%), whereas persistent dysgeusia was identified in 130 cases among 1,887 COVID-19 survivors (7.04%, 95% CI: 5.96%-8.30%). Data was insufficient to assess the relationship between COVID-19 severity and the occurrence of all prolonged GI symptoms. Conclusion: Persistent GI symptoms among COVID-19 survivors after discharge or recovery raises a concern regarding the long-term impact of the COVID-19 infection on the quality of life of the survivors. Despite several potential explanations proposed, studies that aim to follow patients after recovery from COVID-19 and determine the pathogenesis of the prolonged symptoms of COVID-19 survivors are warranted. PROSPERO registration: CRD42021239187.
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Affiliation(s)
- Fauzi Yusuf
- Division of Gastroenterohepatology, Department of Internal
Medicine, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Aceh, 23111,
Indonesia
- Division of Gastroenterohepatology, Department of Internal
Medicine, Dr. Zainoel Abidin Hospital, Banda Aceh, Aceh, 23126, Indonesia
| | - Marhami Fahriani
- Medical Research Unit, School of Medicine, Universitas Syiah
Kuala, Banda Aceh, Aceh, 23111, Indonesia
| | - Sukamto S. Mamada
- Faculty of Pharmacy, Hasanuddin University, Makassar, South
Sulawesi, 90245, Indonesia
| | - Andri Frediansyah
- Research Division for Natural Product Technology (BPTBA),
Indonesian Institute of Sciences (LIPI), Wonosari, 55861, Indonesia
| | - Azzaki Abubakar
- Division of Gastroenterohepatology, Department of Internal
Medicine, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Aceh, 23111,
Indonesia
- Division of Gastroenterohepatology, Department of Internal
Medicine, Dr. Zainoel Abidin Hospital, Banda Aceh, Aceh, 23126, Indonesia
| | - Desi Maghfirah
- Division of Gastroenterohepatology, Department of Internal
Medicine, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Aceh, 23111,
Indonesia
- Division of Gastroenterohepatology, Department of Internal
Medicine, Dr. Zainoel Abidin Hospital, Banda Aceh, Aceh, 23126, Indonesia
| | - Jonny Karunia Fajar
- Medical Research Unit, School of Medicine, Universitas Syiah
Kuala, Banda Aceh, Aceh, 23111, Indonesia
- Brawijaya Internal Medicine Research Center, Department of
Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, East
Java, 65145, Indonesia
| | | | - Muhammad Ilmawan
- Faculty of Medicine, Universitas Brawijaya, Malang, East Java,
65117, Indonesia
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh,
Chittagong, 4381, Bangladesh
| | - Youdiil Ophinni
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139,
USA
| | | | - Sri Masyeni
- Department of Internal Medicine, Faculty of Medicine and Health
Sciences, Universitas Warmadewa, Bali, Indonesia
- Department of Internal Medicine, Sanjiwani Hospital, Bali,
Indonesia
| | - Abdulla Salem Bin Ghouth
- Department of Community Medicine, Hadhramout University College
of Medicine, Mukalla, Yemen
- Ministry of Public Health and Population, Sana'a, Yemen
| | - Hanifah Yusuf
- Department of Pharmacology, School of Medicine, Universitas
Syiah Kuala, Banda Aceh, Aceh, 23111, Indonesia
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research
Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India
| | - Firzan Nainu
- Faculty of Pharmacy, Hasanuddin University, Makassar, South
Sulawesi, 90245, Indonesia
| | - Harapan Harapan
- Medical Research Unit, School of Medicine, Universitas Syiah
Kuala, Banda Aceh, Aceh, 23111, Indonesia
- Department of Microbiology, School of Medicine, Universitas
Syiah Kuala, Banda Aceh, Aceh, 23111, Indonesia
- Tropical Disease Centre, School of Medicine, Universitas Syiah
Kuala, Banda Aceh, Aceh, 23111, Indonesia
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Westerink F, Huibregtse I, De Hoog M, Bruin S, Meesters E, Brandjes D, Gerdes V. Faecal Inflammatory Biomarkers and Gastrointestinal Symptoms after Bariatric Surgery: A Longitudinal Study. Inflamm Intest Dis 2021; 6:109-116. [PMID: 34124182 DOI: 10.1159/000514576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/29/2020] [Indexed: 11/19/2022] Open
Abstract
Background Bariatric surgery induces various gastrointestinal (GI) modifications. We performed the first study longitudinally assessing the effect of bariatric surgery on faecal inflammatory biomarker levels and its relation with GI complaints. Method Faecal calprotectin, lactoferrin, and calgranulin-C levels were determined in 41 patients (34 Roux-en-Y [RYGB], 7 sleeves) before and at 6-16 weeks, 6 months, and 1 year after surgery. Changes in biomarker levels and percentage of patients above reference value were determined. Gastrointestinal symptom rating scale (GSRS) was used to assess GI complaints at corresponding time points. The postoperative relation between GSRS score and biomarker levels above reference value was investigated. Results After RYGB, median calprotectin levels are significantly higher (>188, 104-415 μg/g) than before surgery (40, 19-78 μg/g; p < 0.001), and over 90% of patients have levels above reference value 1 year after surgery. Median lactoferrin was 0.4 (0.2-1.6) μg/g before, and >5.9 (1.8-13.6) μg/g after surgery (p < 0.001). Median calgranulin-C levels remained far below the reference value and were 0.13 (0.05-0.24) μg/g before and <0.23 (0.06-0.33) μg/g after surgery. Similar results were found after sleeve gastrectomy. No difference was seen in GSRS score for patients with calprotectin and lactoferrin levels above reference values. Conclusion Faecal inflammatory biomarkers calprotectin and lactoferrin, but not calgranulin-C, rise above reference values shortly after bariatric surgery and remain elevated in the majority of patients. The discrepancy between calprotectin and calgranulin-C levels suggests no GI inflammation. Furthermore, patients after RYGB with biomarkers above the population reference value do not seem to have more GI complaints.
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Affiliation(s)
- Floris Westerink
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Inge Huibregtse
- Department of gastroenterology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands
| | | | - Sjoerd Bruin
- Department of surgery, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | - Eelco Meesters
- Department of internal medicine, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | - Desiderius Brandjes
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Victor Gerdes
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands.,Department of internal medicine, Spaarne Gasthuis, Hoofddorp, The Netherlands
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29
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Patel C, Keller L, Welsche S, Hattendorf J, Sayasone S, Ali SM, Ame SM, Coulibaly JT, Hürlimann E, Keiser J. Assessment of fecal calprotectin and fecal occult blood as point-of-care markers for soil-transmitted helminth attributable intestinal morbidity in a case-control substudy conducted in Côte d'Ivoire, Lao PDR and Pemba Island, Tanzania. EClinicalMedicine 2021; 32:100724. [PMID: 33554091 PMCID: PMC7851339 DOI: 10.1016/j.eclinm.2021.100724] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/06/2021] [Accepted: 01/07/2021] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Infections with soil-transmitted helminths (STHs) may result in chronic inflammatory disorders affecting the human host. The objective of this study was to evaluate Fecal Calprotectin (FC) and Fecal Occult Blood (FOB) in individuals infected and non-infected with STHs to identify potential intestinal morbidity markers. METHODS Stool from participants diagnosed positive for Trichuris trichiura and concomitant STH infections from three countries was used to perform FC and FOB point-of-care assays. Simultaneously, identified STH negative participants underwent FC and FOB testing as controls. Potential associations between test results and determinants were analyzed using multivariable logistic regression. FINDINGS In total, 1034 T. trichiura infected cases (mostly light infections) and 157 STH negative controls were tested for FC and FOB. Among all participants tested, 18·5% had ≥ 50 µg/g FC concentration, while 14 (1·2%) were positive for FOB. No statistically significant association was found between T. trichiura infection or Ascaris lumbricoides co-infection and FC concentration, while an inverse association (odds ratio (OR): 0·45, 95% credible intervals (CrI): 0·26, 0·75) was found between hookworm co-infection and FC concentration. In Lao PDR, the proportion of participants in the ≥ 50 µg/g FC category was significantly higher in the oldest age category compared to the 5-11 years group (OR: 3·31, 95% CrI: 1·62, 7·24). Too few participants were found positive for FOB to derive any conclusions. INTERPRETATION Studies are needed to better understand the relationship between intestinal morbidity and STH infections. Suitable, standardized, low-cost markers of STH attributable morbidity to better monitor the impact of STH control interventions are necessary. FUNDING BMGF (OPP1153928).
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Affiliation(s)
- Chandni Patel
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Ladina Keller
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Sophie Welsche
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Jan Hattendorf
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Somphou Sayasone
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
- Department of International Program for Health in the Tropics, Lao Tropical and Public Health Institute, Vientiane, Lao People's Democratic Republic
| | - Said M. Ali
- Public Health Laboratory Ivo de Carneri, Chake Chake, Pemba, Zanzibar, Tanzania
| | - Shaali M. Ame
- Public Health Laboratory Ivo de Carneri, Chake Chake, Pemba, Zanzibar, Tanzania
| | - Jean Tenena Coulibaly
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
- Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire
- Department of Research and Development, Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire
| | - Eveline Hürlimann
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Jennifer Keiser
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
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30
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Willers M, Ulas T, Völlger L, Vogl T, Heinemann AS, Pirr S, Pagel J, Fehlhaber B, Halle O, Schöning J, Schreek S, Löber U, Essex M, Hombach P, Graspeuntner S, Basic M, Bleich A, Cloppenborg-Schmidt K, Künzel S, Jonigk D, Rupp J, Hansen G, Förster R, Baines JF, Härtel C, Schultze JL, Forslund SK, Roth J, Viemann D. S100A8 and S100A9 Are Important for Postnatal Development of Gut Microbiota and Immune System in Mice and Infants. Gastroenterology 2020; 159:2130-2145.e5. [PMID: 32805279 DOI: 10.1053/j.gastro.2020.08.019] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 07/14/2020] [Accepted: 08/09/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS After birth, the immune system matures via interactions with microbes in the gut. The S100 calcium binding proteins S100A8 and S100A9, and their extracellular complex form, S100A8-A9, are found in high amounts in human breast milk. We studied levels of S100A8-A9 in fecal samples (also called fecal calprotectin) from newborns and during infancy, and their effects on development of the intestinal microbiota and mucosal immune system. METHODS We collected stool samples (n = 517) from full-term (n = 72) and preterm infants (n = 49) at different timepoints over the first year of life (days 1, 3, 10, 30, 90, 180, and 360). We measured levels of S100A8-A9 by enzyme-linked immunosorbent assay and analyzed fecal microbiomes by 16S sRNA gene sequencing. We also obtained small and large intestine biopsies from 8 adults and 10 newborn infants without inflammatory bowel diseases (controls) and 8 infants with necrotizing enterocolitis and measured levels of S100A8 by immunofluorescence microscopy. Children were followed for 2.5 years and anthropometric data and medical information on infections were collected. We performed studies with newborn C57BL/6J wild-type and S100a9-/- mice (which also lack S100A8). Some mice were fed or given intraperitoneal injections of S100A8 or subcutaneous injections of Staphylococcus aureus. Blood and intestine, mesenterial and celiac lymph nodes were collected; cells and cytokines were measured by flow cytometry and studied in cell culture assays. Colon contents from mice were analyzed by culture-based microbiology assays. RESULTS Loss of S100A8 and S100A9 in mice altered the phenotypes of colonic lamina propria macrophages, compared with wild-type mice. Intestinal tissues from neonatal S100-knockout mice had reduced levels of CX3CR1 protein, and Il10 and Tgfb1 mRNAs, compared with wild-type mice, and fewer T-regulatory cells. S100-knockout mice weighed 21% more than wild-type mice at age 8 weeks and a higher proportion developed fatal sepsis during the neonatal period. S100-knockout mice had alterations in their fecal microbiomes, with higher abundance of Enterobacteriaceae. Feeding mice S100 at birth prevented the expansion of Enterobacteriaceae, increased numbers of T-regulatory cells and levels of CX3CR1 protein and Il10 mRNA in intestine tissues, and reduced body weight and death from neonatal sepsis. Fecal samples from term infants, but not preterm infants, had significantly higher levels of S100A8-A9 during the first 3 months of life than fecal samples from adults; levels decreased to adult levels after weaning. Fecal samples from infants born by cesarean delivery had lower levels of S100A8-A9 than from infants born by vaginal delivery. S100 proteins were expressed by lamina propria macrophages in intestinal tissues from infants, at higher levels than in intestinal tissues from adults. High fecal levels of S100 proteins, from 30 days to 1 year of age, were associated with higher abundance of Actinobacteria and Bifidobacteriaceae, and lower abundance of Gammaproteobacteria-particularly opportunistic Enterobacteriaceae. A low level of S100 proteins in infants' fecal samples associated with development of sepsis and obesity by age 2 years. CONCLUSION S100A8 and S100A9 regulate development of the intestinal microbiota and immune system in neonates. Nutritional supplementation with these proteins might aide in development of preterm infants and prevent microbiota-associated disorders in later years.
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Affiliation(s)
- Maike Willers
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Thomas Ulas
- Genomics and Immunoregulation, LIMES-Institute, University of Bonn, Bonn, Germany; PRECISE, Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany
| | - Lena Völlger
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Thomas Vogl
- Institute of Immunology, University of Münster, Münster, Germany
| | - Anna S Heinemann
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Sabine Pirr
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Julia Pagel
- Department of Pediatrics, University of Lübeck, Lübeck, Germany
| | - Beate Fehlhaber
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Olga Halle
- Institute of Immunology, Hannover Medical School, Hannover, Germany
| | - Jennifer Schöning
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Sabine Schreek
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Ulrike Löber
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Morgan Essex
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Peter Hombach
- Genomics and Immunoregulation, LIMES-Institute, University of Bonn, Bonn, Germany
| | - Simon Graspeuntner
- Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany
| | - Marijana Basic
- Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany
| | - Andre Bleich
- Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany
| | | | - Sven Künzel
- Max Planck Institute for Evolutionary Biology, Plön, Germany
| | - Danny Jonigk
- Department of Pathology, Hannover Medical School, Hannover, Germany
| | - Jan Rupp
- Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany
| | - Gesine Hansen
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Reinhold Förster
- Institute of Immunology, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - John F Baines
- Institute of Experimental Medicine, University of Kiel, Kiel, Germany; Max Planck Institute for Evolutionary Biology, Plön, Germany
| | - Christoph Härtel
- PRIMAL Consortium, Hannover Medical School, Hannover, Germany; Department of Pediatrics, University Hospital of Würzburg, Würzburg, Germany
| | - Joachim L Schultze
- Genomics and Immunoregulation, LIMES-Institute, University of Bonn, Bonn, Germany; PRECISE, Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany
| | - Sofia K Forslund
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany; European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany
| | - Johannes Roth
- Institute of Immunology, University of Münster, Münster, Germany
| | - Dorothee Viemann
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany; PRIMAL Consortium, Hannover Medical School, Hannover, Germany.
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31
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Leite Dantas R, Bettenworth D, Varga G, Weinhage T, Wami HT, Dobrindt U, Roth J, Vogl T, Ludwig S, Wixler V. Spontaneous onset of TNFα-triggered colonic inflammation depends on functional T lymphocytes, S100A8/A9 alarmins, and MHC H-2 haplotype. J Pathol 2020; 251:388-399. [PMID: 32449525 DOI: 10.1002/path.5473] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 05/05/2020] [Accepted: 05/18/2020] [Indexed: 12/17/2022]
Abstract
Recently, we established a doxycycline-inducible human tumor necrosis factor alpha (TNFα)-transgenic mouse line, ihTNFtg. Non-induced young and elderly mice showed low but constitutive expression of hTNFα due to promoter leakiness. The persistently present hTNFα stimulated endogenous pro-inflammatory mouse mS100A8/A9 alarmins. Secreted mS100A8/A9 in turn induced the expression and release of mouse mTNFα. The continuous upregulation of pro-inflammatory mTNFα and mS100A8/A9 proteins, due to their mutual expression dependency, gradually led to increased levels in colon tissue and blood. This finally exceeded the threshold levels tolerated by the healthy organism, leading to the onset of intestinal inflammation. Here, recombinant hTNFα functioned as an initial trigger for the development of chronic inflammation. Crossing ihTNFtg mice with S100A9KO mice lacking active S100A8/A9 alarmins or with Rag1KO mice lacking T and B lymphocytes completely abrogated the development of colonic inflammation, despite the still leaky hTNFα promoter. Furthermore, both the intensity of the immune response and the strength of immunosuppressive Treg induction was found to depend on the major histocompatibility complex (MHC) genetic composition. In summary, the onset of intestinal inflammation in elderly mice depends on at least four factors that have to be present simultaneously: TNFα upregulation, S100A8/A9 protein expression, functional T lymphocytes and genetic composition, with the MHC haplotype being of central importance. Only joint action of these factors leads to chronic intestinal inflammation, while absence of any of these determinants abrogates the development of the autoimmune disorder. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Rafael Leite Dantas
- Institute of Molecular Virology, Westfaelische Wilhelms University, Muenster, Germany
| | - Dominik Bettenworth
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Muenster, Muenster, Germany
| | - Georg Varga
- Pediatric Rheumatology and Immunology, Westfaelische Wilhelms University, Muenster, Germany
| | - Toni Weinhage
- Pediatric Rheumatology and Immunology, Westfaelische Wilhelms University, Muenster, Germany
| | | | - Ulrich Dobrindt
- Institute of Hygiene, Westfaelische Wilhelms University, Muenster, Germany
| | - Johannes Roth
- Institute of Immunology, Westfaelische Wilhelms University, Muenster, Germany
| | - Thomas Vogl
- Institute of Immunology, Westfaelische Wilhelms University, Muenster, Germany
| | - Stephan Ludwig
- Institute of Molecular Virology, Westfaelische Wilhelms University, Muenster, Germany
| | - Viktor Wixler
- Institute of Molecular Virology, Westfaelische Wilhelms University, Muenster, Germany
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32
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Fauny M, D'Amico F, Bonovas S, Netter P, Danese S, Loeuille D, Peyrin-Biroulet L. Faecal Calprotectin for the Diagnosis of Bowel Inflammation in Patients With Rheumatological Diseases: A Systematic Review. J Crohns Colitis 2020; 14:688-693. [PMID: 31858121 DOI: 10.1093/ecco-jcc/jjz205] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Endoscopic and histological gut inflammation are present in half of patients with ankylosing spondylitis [AS] or spondyloarthritis [SpA]. We performed a systematic literature review on the use of faecal calprotectin [FC] in patients with rheumatic diseases. METHODS Searches of the PubMed, Web of Science, and Cochrane Library databases were performed up to September 2019 to identify all studies including adult patients with confirmed diagnosis of SpA or AS. RESULTS Seven studies met the inclusion criteria: six prospective observational studies and one retrospective observational study. Study populations consisted of SpA patients in four studies and AS patients in three studies. In six studies, an ELISA test was used for FC levels and in one case, a semi-quantitative assay was adopted. In all included studies, patients with SpA or AS had elevated FC levels, ranging from 21.2% to 70.7% of patients. In six studies, patients with increased FC levels had macroscopic mucosal inflammation, ranging from 11% to 80% of cases. Four studies highlighted the presence of microscopic alterations in patients with high FC levels, ranging from 41.7% to 100% of patients. An FC cut-off level predicting the inflammatory bowel disease [IBD] occurrence was found in two studies: 266 mg/kg and 132 mg/kg, with sensitivity and specificity of 100%, 78.7% and 66.7%, 76.9%, respectively. CONCLUSIONS Faecal calprotectin is a useful and non-invasive marker to predict IBD in patients with SpA or AS. Gut histological and macroscopic mucosal inflammation were found in up to 100% and 80% of rheumatological patients with increased FC levels.
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Affiliation(s)
- Marine Fauny
- Rheumatology Department, University Hospital of Nancy, Nancy, France
| | - Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology and Inserm NGERE U1256, University of Lorraine, Nancy University Hospital, Vandoeuvre-lès-Nancy, France
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology, Humanitas Research Hospital, Milan, Italy
| | - Patrick Netter
- Ingénierie Moléculaire et Ingénierie Articulaire [IMoPA]. UMR-7365 CNRS, University of Lorraine and University Hospital of Nancy, Nancy, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology, Humanitas Research Hospital, Milan, Italy
| | - Damien Loeuille
- Rheumatology Department, University Hospital of Nancy, Nancy, France.,Ingénierie Moléculaire et Ingénierie Articulaire [IMoPA]. UMR-7365 CNRS, University of Lorraine and University Hospital of Nancy, Nancy, France
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University of Lorraine, Nancy University Hospital, Vandoeuvre-lès-Nancy, France
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33
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Ribaldone DG, Brigo S, Mangia M, Saracco GM, Astegiano M, Pellicano R. Oral Manifestations of Inflammatory Bowel Disease and the Role of Non-Invasive Surrogate Markers of Disease Activity. MEDICINES (BASEL, SWITZERLAND) 2020; 7:33. [PMID: 32560118 PMCID: PMC7345678 DOI: 10.3390/medicines7060033] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 06/03/2020] [Accepted: 06/15/2020] [Indexed: 12/17/2022]
Abstract
Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), can be associated with several extra-intestinal manifestations requiring a multidisciplinary management both in terms of work-up and therapy. Oral lesions are common in patients with IBD, with a prevalence ranging from 5% to 50%. These can represent an oral location of IBD as well as a side-effect of drugs used to treat the intestinal disease. Oral manifestations, occurring in patients with IBD, can be divided in nonmalignant, specific, and non-specific ones, and malignant lesions. While there is undoubtedly a need to search for an IBD in patients with oral lesions associated with intestinal symptoms, the work-up of those with an exclusive oral lesion should be personalized. Fecal calprotectin is a non-invasive marker of intestinal inflammation and may be used to select which patients need to undergo endoscopic examination, thereby avoiding unnecessary investigations. The pharmacological armamentarium to treat oral lesions associated with IBD includes topical or systemic corticosteroids, immunosuppressive agents, and biologic drugs.
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Affiliation(s)
| | - Selvaggia Brigo
- Bow Lane Dental Group, St George’s Hospital, Bupa Dental Care, London SW17 0QT, UK;
| | - Michela Mangia
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (M.M.); (G.M.S.)
| | - Giorgio Maria Saracco
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (M.M.); (G.M.S.)
| | - Marco Astegiano
- Unit of Gastroenterology, Molinette Hospital, 10126 Turin, Italy; (M.A.); (R.P.)
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette Hospital, 10126 Turin, Italy; (M.A.); (R.P.)
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Bramhall M, Rich K, Chakraborty A, Logunova L, Han N, Wilson J, McLaughlin J, Brass A, Cruickshank SM. Differential Expression of Soluble Receptor for Advanced Glycation End-products in Mice Susceptible or Resistant to Chronic Colitis. Inflamm Bowel Dis 2020; 26:360-368. [PMID: 31840738 PMCID: PMC7012299 DOI: 10.1093/ibd/izz311] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Identifying the factors that contribute to chronicity in inflamed colitic tissue is not trivial. However, in mouse models of colitis, we can investigate at preclinical timepoints. We sought to validate murine Trichuris muris infection as a model for identification of factors that promote development of chronic colitis. METHODS We compared preclinical changes in mice with a resolving immune response to T. muris (resistant) vs mice that fail to expel the worms and develop chronic colitis (susceptible). Findings were then validated in healthy controls and patients with suspected or confirmed IBD. RESULTS The receptor for advanced glycation end products (RAGE) was highly dysregulated between resistant and susceptible mice before the onset of any pathological signs. Increased soluble RAGE (sRAGE) in the serum and feces of resistant mice correlated with reduced colitis scores. Mouse model findings were validated in a preliminary clinical study: fecal sRAGE was differentially expressed in patients with active IBD compared with IBD in remission, patients with IBD excluded, or healthy controls. CONCLUSIONS Preclinical changes in mouse models can identify early pathways in the development of chronic inflammation that human studies cannot. We identified the decoy receptor sRAGE as a potential mechanism for protection against chronic inflammation in colitis in mice and humans. We propose that the RAGE pathway is clinically relevant in the onset of chronic colitis and that further study of sRAGE in IBD may provide a novel diagnostic and therapeutic target.
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Affiliation(s)
- Michael Bramhall
- Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK
| | - Kevin Rich
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK
| | - Ajanta Chakraborty
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK
| | - Larisa Logunova
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK
| | - Namshik Han
- Manchester Academic Health Science Centre, School of Medical Sciences, The University of Manchester, Manchester, UK
- Milner Therapeutics Institute, University of Cambridge, Cambridge, UK
| | | | - John McLaughlin
- Salford Royal NHS Foundation Trust, Salford, UK
- Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK
| | - Andy Brass
- Manchester Academic Health Science Centre, School of Medical Sciences, The University of Manchester, Manchester, UK
| | - Sheena M Cruickshank
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK
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35
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Bermejo F, Algaba A, Bonillo D, Jiménez L, Guardiola-Arévalo A, Pacheco M, Castaño Á, Guerra I. Limitations of the determination of faecal calprotectin in patients with ulcerative colitis and inflammatory polyps. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:73-78. [PMID: 31648810 DOI: 10.1016/j.gastrohep.2019.08.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 07/10/2019] [Accepted: 08/22/2019] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Faecal calprotectin is a useful technique for detecting activity in patients with ulcerative colitis. However, there may be high levels due to factors other than the activity of ulcerative colitis. Our aim was to analyse possible false positive results of calprotectin for the activity of ulcerative colitis owing to the presence of inflammatory polyps. PATIENTS AND METHODS Retrospective, observational, descriptive study. Data was collected from patients monitored for 2 years in whom a colonoscopy had been requested within 3 months after detecting high calprotectin values (>150μg/g) and before modifying the treatment. RESULTS We reviewed 39 patients and in 5 of them, with previous diagnosis of extensive ulcerative colitis, inflammatory polyps were detected. Three patients were on treatment with mesalazine, one with azathioprine and other with infliximab. All of them were asymptomatic and the endoscopy did not show macroscopic activity (endoscopic Mayo score=0) or histological activity. The median values of calprotectin were 422μg/g (IQR: 298-2,408) and they remained elevated in a second measurement. In 4 of the patients the inflammatory polyps were multiple and small in size. The other patient had a polyp measuring 4cm. DISCUSSION In clinical practice we can find high faecal calprotectin levels not due to the presence of ulcerative colitis activity, but due to other lesions such as inflammatory polyps. This fact must be taken into account before carrying out relevant changes such as step-up therapy to immunosuppressive drugs or biological drugs in patients with confirmed high calprotectin levels.
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Affiliation(s)
- Fernando Bermejo
- Servicio de Digestivo, Hospital Universitario de Fuenlabrada, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, España; Departamento de Medicina, Universidad Rey Juan Carlos, Madrid, España.
| | - Alicia Algaba
- Servicio de Digestivo, Hospital Universitario de Fuenlabrada, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, España
| | - Daniel Bonillo
- Servicio de Digestivo, Hospital Universitario de Fuenlabrada, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, España
| | - Laura Jiménez
- Servicio de Digestivo, Hospital Universitario de Fuenlabrada, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, España
| | - Antonio Guardiola-Arévalo
- Servicio de Digestivo, Hospital Universitario de Fuenlabrada, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, España
| | - María Pacheco
- Servicio de Laboratorio, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
| | - Ángel Castaño
- Servicio de Anatomía Patológica, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
| | - Iván Guerra
- Servicio de Digestivo, Hospital Universitario de Fuenlabrada, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, España
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Cozijnsen MA, Ben Shoham A, Kang B, Choe BH, Choe YH, Jongsma MME, Russell RK, Ruemmele FM, Escher JC, de Ridder L, Koletzko S, Martín-de-Carpi J, Hyams J, Walters T, Griffiths A, Turner D. Development and Validation of the Mucosal Inflammation Noninvasive Index For Pediatric Crohn's Disease. Clin Gastroenterol Hepatol 2020; 18:133-140.e1. [PMID: 30981008 DOI: 10.1016/j.cgh.2019.04.012] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 04/04/2019] [Accepted: 04/05/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Mucosal healing (MH) has become a goal of therapy for Crohn's disease (CD), but frequent endoscopies are not feasible. We aimed to develop and validate a non-invasive index to assess mucosal inflammation in children with CD. METHODS We collected data from the multi-center prospective ImageKids study, in which children with CD underwent ileocolonoscopy with magnetic resonance enterography. We investigated the association of pediatric CD activity index (PCDAI) items and laboratory test results with the simple endoscopic score for CD (SESCD). We used these data in a blended mathematical judgmental clinimetric approach to develop a weighted categorized index to identify children with CD who have MH, which we called the MINI index. We validated the index using data from 3 independent patient cohorts. The derivation and validation cohorts included 154 and 168 children, respectively (age 14.1 ± 2.5 years and 14.2 ± 3.9 years), of whom 16% and 36% had MH (defined as SESCD<3). RESULTS In multivariable models, the stooling item of the PCDAI, erythrocyte sedimentation rate, and level of fecal calprotectin were associated with SESCD (all P < .05). We added data on level of C-reactive protein to develop the MINI index. MINI scores below 8 identified children with MH with 88% sensitivity and 85% specificity in the derivation cohort and with 84% sensitivity and 87% specificity in the validation cohorts. Ninety percent of the patients in the validation cohort with scores of 8 or more had active mucosal inflammation, yet 78% of patients with scores below 8 had MH. Scores below 6 increase the positive predictive value to 86%. CONCLUSIONS We developed an index to non-invasively assess mucosal inflammation in children with CD. This index, identifies children with MH with high sensitivity and specificity. The added benefit of MINI over measurement of fecal calprotectin was small but significant, especially for patients with concentrations of fecal calprotectin from 100 to 599 μg/g. ClinicalTrials.gov no: NCT01881490.
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Affiliation(s)
| | | | - Ben Kang
- Kyungpook National University Children's Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Byung-Ho Choe
- Kyungpook National University Children's Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yon Ho Choe
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | | | | | - Frank M Ruemmele
- Université Paris Descartes - Sorbonne Paris Cité, APHP- Hôpital Necker Enfants Malades, Service de Gastroentérologie, Paris, France
| | - Johanna C Escher
- Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Lissy de Ridder
- Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands
| | | | | | - Jeffrey Hyams
- Connecticut Children's Medical Center, Hartford, Connecticut
| | | | | | - Dan Turner
- Shaare Zedek Medical Center, the Hebrew University of Jerusalem, Israel.
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Bridges CS, Grützner N, Suchodolski JS, Steiner JM, Heilmann RM. Analytical validation of an enzyme-linked immunosorbent assay for the quantification of S100A12 in the serum and feces of cats. Vet Clin Pathol 2019; 48:754-761. [PMID: 31820477 DOI: 10.1111/vcp.12812] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Revised: 04/29/2019] [Accepted: 05/01/2019] [Indexed: 11/30/2022]
Abstract
BACKGROUND Measuring S100A12 concentrations in serum and feces is a sensitive and specific marker of inflammation, such as seen with chronic gastrointestinal inflammation in people and dogs. Biomarkers of inflammation in cats are currently lacking. OBJECTIVES We aimed to analytically cross-validate the canine S100A12-ELISA for the measurement of S100A12 in feline specimens. METHODS The ELISA was analytically validated by assessing dilutional linearity, spiking/recovery, intra- and inter-assay variability. Reference intervals for serum and fecal feline S100A12 concentrations were calculated using samples from healthy cats, and the short-term biological variation of fecal S100A12 was assessed. RESULTS Observed-to-expected ratios (O/E) for serial dilutions of serum and fecal extracts ranged from 91%-159% (mean, 120%) and 100%-128% (mean, 114%), and for the spiking/recovery method ranged from 106%-263% (mean, 154%) and 52%-171% (mean, 112%). Intra- and inter-assay CV% for serum were ≤5.6% and ≤14.0%, and for fecal extracts were ≤3.8% and ≤19.1%, repsectively. RIs for feline serum and fecal S100A12 concentrations were <43 µg/L and < 20 ng/g, respectively. A mild short-term biologic variation, but large individuality were detected when measuring fecal S100A12 concentrations in healthy cats. CONCLUSIONS The canine S100A12-ELISA is accurate, reproducible, and sufficiently linear and precise for the measurement of S100A12 in feline serum and fecal samples. The use of this assay is a reasonable option for the measurement of S100A12 concentrations in feline specimens and provides a basis for the further evaluation of S100A12 in cats with gastrointestinal disease. Using a population-based RI for fecal feline S100A12 appears to be of limited value.
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Affiliation(s)
- Cory S Bridges
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Niels Grützner
- Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), SA, Germany
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Jörg M Steiner
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Romy M Heilmann
- Department for Small Animals, Veterinary Teaching Hospital, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
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38
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Cerrillo E, Moret I, Iborra M, Pamies J, Hervás D, Tortosa L, Sáez-González E, Nos P, Beltrán B. A Nomogram Combining Fecal Calprotectin Levels and Plasma Cytokine Profiles for Individual Prediction of Postoperative Crohn's Disease Recurrence. Inflamm Bowel Dis 2019; 25:1681-1691. [PMID: 30925193 DOI: 10.1093/ibd/izz053] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aims of this study were to characterize the immune response profile in patients with Crohn's disease (CD) and early postoperative recurrence (POR), to identify predictive biomarkers, and to develop a noninvasive predictive tool for individual estimation of POR risk. METHODS Sixty-one patients who had undergone ileocolonic resection for CD were prospectively included and followed up for 24 months. Fecal calprotectin (FC), analytical parameters, and plasma cytokines were obtained before surgery and at various time points during postoperative follow-up. Morphological recurrence was assessed by ileocolonoscopy or magnetic resonance enterography within 6-12 months after surgery. Clinical activity was scored using the Harvey-Bradshaw Index. RESULTS Twenty-seven patients (44.3%) had morphological recurrence during follow-up. Fecal calprotectin values were significantly associated with POR risk over time. The receiver operating characteristic curve for FC provided an area under the curve (AUC) of 0.88 (95% confidence interval, 0.75-0.96), and morphological recurrence was best predicted by FC ≥160 μg/g at 6 months after surgery (85% sensitivity, 70% specificity, 26% predictive positive value, 98% negative predictive value [NPV]). The plasma cytokine profile showed higher presurgery interleukin (IL)-13 plasma levels and higher IL-6 and interferon (IFN)-γ levels at 6 months after surgery in patients with POR compared with patients without recurrence. The combination of FC, IL-6, and IFN-γ values at 6 months gave an AUC of 0.90 for predicting an early recurrence. CONCLUSIONS FC values <160 μg/g at 6 months have a high NPV to rule out early lesions. Combined values of FC, IL-6, and IFN-γ levels at 6 months postsurgery constitute a prognostic index with a high predictive capacity to assess the risk of early POR.
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Affiliation(s)
- Elena Cerrillo
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Inés Moret
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Marisa Iborra
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - José Pamies
- Radiology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - David Hervás
- Biostatistics Unit, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Luis Tortosa
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Esteban Sáez-González
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Pilar Nos
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Belén Beltrán
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
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39
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Bourgonje AR, Gabriëls RY, de Borst MH, Bulthuis MLC, Faber KN, van Goor H, Dijkstra G. Serum Free Thiols Are Superior to Fecal Calprotectin in Reflecting Endoscopic Disease Activity in Inflammatory Bowel Disease. Antioxidants (Basel) 2019. [PMID: 31480545 DOI: 10.3390/antiox8090351.pmid:31480545;pmcid:pmc6769968] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/30/2023] Open
Abstract
Oxidative stress plays a pivotal role in the pathogenesis of inflammatory bowel diseases (IBD). Serum free thiols (R-SH) reliably reflect systemic oxidative stress, since they are readily oxidized by reactive species. Here, we aimed to establish concentrations of serum free thiols in IBD and assessed their discriminating capacity regarding endoscopic disease activity. Albumin-adjusted serum free thiol concentrations were measured in 78 IBD patients (31 Crohn's disease (CD) and 47 ulcerative colitis (UC) patients) and 50 healthy controls and analyzed for associations with disease parameters and their discriminative value regarding endoscopic disease activity (n = 54) or fecal calprotectin (n = 36) in patients for which those data were available. Mean serum free thiol concentrations were significantly lower in both CD and UC as compared to healthy controls (19.4 ± 3.1 and 17.8 ± 3.4 vs. 21.1 ± 1.9 µmol/g albumin, P < 0.001). Free thiols highly accurately discriminated between mild and moderate-to-severe disease activity, better than fecal calprotectin (FC) levels (AUC = 0.87, P < 0.001 vs. AUC = 0.76, P < 0.05, respectively) and this was maintained after cross-validation (AUC = 0.89, P < 0.001). Serum free thiols are reduced in IBD as compared to healthy controls and strongly correlate with the degree of endoscopic disease activity. Quantifying systemic redox status in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity.
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Affiliation(s)
- Arno R Bourgonje
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
| | - Ruben Y Gabriëls
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
| | - Martin H de Borst
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
| | - Marian L C Bulthuis
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
| | - Klaas Nico Faber
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
| | - Harry van Goor
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
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Serum Free Thiols Are Superior to Fecal Calprotectin in Reflecting Endoscopic Disease Activity in Inflammatory Bowel Disease. Antioxidants (Basel) 2019; 8:antiox8090351. [PMID: 31480545 PMCID: PMC6769968 DOI: 10.3390/antiox8090351] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 08/13/2019] [Accepted: 08/23/2019] [Indexed: 12/19/2022] Open
Abstract
Oxidative stress plays a pivotal role in the pathogenesis of inflammatory bowel diseases (IBD). Serum free thiols (R-SH) reliably reflect systemic oxidative stress, since they are readily oxidized by reactive species. Here, we aimed to establish concentrations of serum free thiols in IBD and assessed their discriminating capacity regarding endoscopic disease activity. Albumin-adjusted serum free thiol concentrations were measured in 78 IBD patients (31 Crohn's disease (CD) and 47 ulcerative colitis (UC) patients) and 50 healthy controls and analyzed for associations with disease parameters and their discriminative value regarding endoscopic disease activity (n = 54) or fecal calprotectin (n = 36) in patients for which those data were available. Mean serum free thiol concentrations were significantly lower in both CD and UC as compared to healthy controls (19.4 ± 3.1 and 17.8 ± 3.4 vs. 21.1 ± 1.9 µmol/g albumin, P < 0.001). Free thiols highly accurately discriminated between mild and moderate-to-severe disease activity, better than fecal calprotectin (FC) levels (AUC = 0.87, P < 0.001 vs. AUC = 0.76, P < 0.05, respectively) and this was maintained after cross-validation (AUC = 0.89, P < 0.001). Serum free thiols are reduced in IBD as compared to healthy controls and strongly correlate with the degree of endoscopic disease activity. Quantifying systemic redox status in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity.
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41
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Brechmann T, Günther K, Neid M, Tannapfel A, Schmiegel W. Phenotype of histologically suspected drug-induced colitis; results of a comparative, retrospective cohort study. Scand J Gastroenterol 2019; 54:855-862. [PMID: 31215277 DOI: 10.1080/00365521.2019.1630674] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background/aims: Drug-induced colitis (DiC) is a rarely reported form of colonopathy and data about the clinical and endoscopic characteristics are scarce. The aim was to investigate the phenotype of DiC. Methods: Patients in a retrospective case control study were assigned to either DiC or one of two age- and gender-matched control groups (non-inflammatory controls and inflammatory colitis from other causes) based on histopathological findings. Patients' basic characteristics, symptoms, biochemical results and endoscopic appearance were collected. Statistical analysis included ANOVA, the chi-squared test and two-tailed t-test. Results: A total of 211 patients with DiC were included (97 males, age 62.1 ± 16.1 years, BMI 25.9 ± 6.1 kg m-2). In comparison to both control groups, DiC patients presented higher ASA and ECOG-scores and more particularly atherosclerotic comorbidities. The most abundant symptoms were abdominal pain (51.8%), diarrhoea (50.7%) and haematochezia (24.3%). The red blood cell count demarcated anaemia (12.7 ± 2.3 mg/dl) and C-reactive protein was slightly elevated (2.7 ± 5.2 mg/dl). The endoscopic features included erythema (46.9%), oedema (29.9%), erosions (29.9%) and ulcers (14.7%). The inflammation affected the rectum rarely (2.4%) but affected the rest of the colon without predilection in a segmental manner (p<.05). The severity of DiC was mostly mild (85.7%). Conclusions: The phenotype of DiC differs slightly from that of colitis from other causes. Taking the clinical features into account might help to confirm drug-induced aetiology once the pathologist has raised the suspicion.
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Affiliation(s)
- Thorsten Brechmann
- Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH , Bochum , Germany
| | - Katharina Günther
- Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH , Bochum , Germany
| | - Matthias Neid
- Institute of Pathology, Ruhr-University , Bochum , Germany
| | | | - Wolff Schmiegel
- Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH , Bochum , Germany
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus , Bochum , Germany
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Heilmann RM, Nestler J, Schwarz J, Grützner N, Ambrus A, Seeger J, Suchodolski JS, Steiner JM, Gurtner C. Mucosal expression of S100A12 (calgranulin C) and S100A8/A9 (calprotectin) and correlation with serum and fecal concentrations in dogs with chronic inflammatory enteropathy. Vet Immunol Immunopathol 2019; 211:64-74. [PMID: 31084897 DOI: 10.1016/j.vetimm.2019.04.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 03/24/2019] [Accepted: 04/14/2019] [Indexed: 12/23/2022]
Abstract
S100A12 and S100A8/A9 (calprotectin) are released from activated mononuclear cells and belong to the group of damage associated molecular patterns. Fecal S100A12 and S100A8/A9 concentrations have been suggested as biomarkers of intestinal inflammation in dogs with chronic inflammatory enteropathies (CIE). However, the mucosal cellular infiltrate in dogs with CIE is primarily lymphocytic-plasmacytic. Whether fecal S100A12 and S100A8/A9 levels reflect the number and/or activity of intestinal mucosal mononuclear cells, or whether these proteins are also produced by other cells has not been investigated. Thus, the aim of this study was to evaluate intestinal mucosal S100A12 and S100A8/A9 positivity and a potential relationship with the respective protein concentrations in serum and fecal samples in dogs with CIE. Serum (single sample), fecal samples (from 3 consecutive days), and gastrointestinal tissue biopsies (i.e., stomach, duodenum, ileum, and colon) were evaluated from 21 dogs with CIE. Serum and fecal S100A12 and S100A8/A9 concentrations were measured by analytically validated in-house ELISAs. Tissue biopsies underwent routine histopathology and immunohistochemical evaluation for S100A12 and S100A8/A9 positivity (S100A12+ and S100A8/A9+, each recorded as positive cells/mm2). S100A12+ and S100A8/A9+ cells were identified in all segments of the gastrointestinal tract, but were predominantly localized in the lamina propria (LP). Duodenal LP S100A12 positivity correlated statistically significantly with that in the stomach and ileum (ρ = 0.66 and 0.69, both p < 0.01), but was inversely correlated with the severity of macrophage infiltration in the duodenum (ρ=-0.47, p = 0.042). Ileal LP S100A8/A9 positivity correlated positively with the extent of ileal neutrophil and macrophage infiltration (ρ=0.61, p = 0.047). Fecal S100A12 concentrations strongly correlated with the number of S100A12+ cells along the entire gastrointestinal tract (ρ = 0.76, p = 0.028), whereas serum S100A12 concentrations were inversely correlated to colonic S100A12+ cell counts (ρ=-0.50, p = 0.043). Mucosal S100A8/A9+ cell counts were not associated with the corresponding fecal or serum S100A8/A9 concentrations. These results suggest that the intestinal mucosa in dogs with CIE contains an increased number of activated (pro-inflammatory) phagocytes expressing and secreting the S100A12 protein, but the macrophage population seen on routine histopathology is predominantly mature (anti-inflammatory) with a reduced or absent expression of S100A12 and a normal or increased expression of S100A8/A9. However, the distribution of intestinal S100A8/A9 expression requires further study.
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Affiliation(s)
- Romy M Heilmann
- Department for Small Animals, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany.
| | - Jasmin Nestler
- Department for Small Animals, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
| | - Jutta Schwarz
- Department for Small Animals, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
| | - Niels Grützner
- Department of Animal Sciences, University of Halle-Wittenberg, Halle, SA, Germany
| | - Andy Ambrus
- Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Johannes Seeger
- Institute of Anatomy, Histology and Embryology, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Jörg M Steiner
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Corinne Gurtner
- Institute of Animal Pathology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, BE, Switzerland
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Maksymowych WP. Biomarkers for Diagnosis of Axial Spondyloarthritis, Disease Activity, Prognosis, and Prediction of Response to Therapy. Front Immunol 2019; 10:305. [PMID: 30899255 PMCID: PMC6416369 DOI: 10.3389/fimmu.2019.00305] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 02/06/2019] [Indexed: 12/21/2022] Open
Abstract
There exists a major unmet need for biomarkers that can identify axial spondyloarthritis (axSpA) early after disease onset because of the availability of highly effective therapies. Several recent reports have examined the autoantibody response in patients with axSpA through the use of protein microarrays and protein-protein interactions although diagnostic performance of biomarkers identified to date has been inadequate. An example of such a biomarker is protein phosphatase magnesium-dependent 1A. Antibodies to the human leukocyte antigen class II-associated invariant chain peptide (anti-CD74) are candidate diagnostic biomarkers but sensitivity declines with increasing duration of disease. Metabolomic studies have employed nuclear magnetic resonance (NMR) spectrometry to identify disease-specific metabolites related to fat metabolism and intestinal microbial metabolism. A second major unmet need exists for biomarkers of disease activity that have superiority over standard C-reactive protein assessment and reflect MRI inflammation in the axial spine. Several biomarkers reflecting inflammation (calprotectin), angiogenesis (vasoactive endothelial growth factor), and connective tissue turnover (C2M, C3M, and citrullinated metalloproteinase degraded fragment of vimentin) have recently been shown to reflect disease activity when compared with clinical outcomes but comparisons with MRI inflammation are very limited. With increasing availability of highly effective but costly therapies, a third unmet need is biomarkers that can predict response to therapies with different mechanisms of action and are superior to C-reactive protein. Calprotectin is currently the only candidate. Although there are as yet no proven therapies for preventing progression of disease there is an unmet need for biomarkers of prognosis that are more responsive than radiography. Aside from CRP no consistent candidates have emerged. Future studies will need to be prospective, include consecutive patients presenting with undiagnosed back pain, and use more reliable and objective endpoints such as MRI inflammation. Moreover, it has become evident that targeted biomarker studies have not been successful in identifying clinically useful biomarkers and technologies that can simultaneously assess “multiomic” markers will need to be analyzed for future advances. These include more sophisticated metabolomic profiling and universal metabolome-standard (UMS) methodology, next generation RNA sequencing, and affinity-based quantitative proteomics based on the use of nucleic acid binders such as the aptamer-based SOMAscan assay.
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Noiseux I, Veilleux S, Bitton A, Kohen R, Vachon L, White Guay B, Rioux JD. Inflammatory bowel disease patient perceptions of diagnostic and monitoring tests and procedures. BMC Gastroenterol 2019; 19:30. [PMID: 30760205 PMCID: PMC6374885 DOI: 10.1186/s12876-019-0946-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 01/29/2019] [Indexed: 02/06/2023] Open
Abstract
Background Inflammatory Bowel Disease (IBD) with its high incidence and prevalence rates in Canada generates a heavy burden of tests and procedures. The purpose of this study is to gain a better understanding of the transfer of information from physician to patient, as well as the patient understanding and perceptions about the tests and procedures that are ordered to them in the context of IBD diagnosis and monitoring. Methods An online questionnaire was completed by 210 IBD patients in Canada. Information on the five most-often used tests or procedures in IBD diagnosis/monitoring was collected. These include: general blood test, colonoscopy, colon biopsy, medical imaging and stool testing. Results The general blood test is both the most ordered and most refused tool. It is also the one with which patients are the least comfortable, the one that generates the least concern and the one about which physicians provide the least information. The stool test is the test/procedure with which patients are the most comfortable. Procedures raise more concerns among patients and physicians provide more information about why they are needed, their impact and the risks they present. Very little information is provided to patients about the risks of having false positives or negative tests. Conclusions This study provides an initial understanding of patient perceptions, the transfer of information from a physician to a patient and a patient’s understanding of the tests and procedures that will be required to treat IBD throughout what is a lifelong disease. The present study takes a first step in better understanding the acceptance of the test or procedure by IBD patients, which is essential for them to adhere to the monitoring process. Electronic supplementary material The online version of this article (10.1186/s12876-019-0946-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Isabelle Noiseux
- Department of Management, Université Laval, Quebec, G1V 0A6, Canada
| | - Sophie Veilleux
- Department of Management, Université Laval, Quebec, G1V 0A6, Canada.
| | - Alain Bitton
- Division of Gastroenterology, McGill University Health Centre, Montreal, H3A 0G4, Canada
| | - Rita Kohen
- Division of Gastroenterology, McGill University Health Centre, Montreal, H3A 0G4, Canada
| | - Luc Vachon
- iGenoMed Consortium, Montreal, H1T 1C8, Canada
| | - Brian White Guay
- Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, H3T 1J4, Canada
| | - John D Rioux
- Department of Medicine, Université de Montréal & Montreal Heart Institute, Montreal, H1T 1C8, Canada
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Riva A, Giacomelli L, Togni S, Franceschi F, Eggenhoffner R, Zuccarini MC, Belcaro G. Oral administration of a lecithin-based delivery form of boswellic acids (Casperome®) for the prevention of symptoms of irritable bowel syndrome: a randomized clinical study. MINERVA GASTROENTERO 2019; 65:30-35. [DOI: 10.23736/s1121-421x.18.02530-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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46
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Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the utility of the determination of faecal calprotectin in inflammatory bowel disease. ACTA ACUST UNITED AC 2018. [DOI: 10.1016/j.gastre.2018.05.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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47
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Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre la utilidad de la determinación de calprotectina fecal en la enfermedad inflamatoria intestinal. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 41:514-529. [DOI: 10.1016/j.gastrohep.2018.05.029] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 05/03/2018] [Accepted: 05/03/2018] [Indexed: 12/14/2022]
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48
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Heilmann RM, Steiner JM. Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs. J Vet Intern Med 2018; 32:1495-1508. [PMID: 30222209 PMCID: PMC6189362 DOI: 10.1111/jvim.15247] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 04/19/2018] [Accepted: 05/24/2018] [Indexed: 12/19/2022] Open
Abstract
Chronic inflammatory enteropathies (CIE) in dogs are a group of disorders that are characterized by chronic persistent or recurrent signs of gastrointestinal disease and histologic evidence of mucosal inflammation. These CIEs are classified as either food-responsive, antibiotic-responsive, or immunosuppressant-responsive enteropathy. Patients not clinically responding to immunomodulatory treatment are grouped as nonresponsive enteropathy and dogs with intestinal protein loss as protein-losing enteropathy. Disease-independent clinical scoring systems were established in dogs for assessment of clinical disease severity and patient monitoring during treatment. Histopathologic and routine clinicopathologic findings are usually not able to distinguish the subgroups of CIE. Treatment trials are often lengthy and further diagnostic tests are usually at least minimally invasive. Biomarkers that can aid in defining the presence of disease, site of origin, severity of the disease process, response to treatment, or a combination of these would be clinically useful in dogs with CIE. This article summarizes the following biomarkers that have been evaluated in dogs with CIE during the last decade, and critically evaluates their potential clinical utility in dogs with CIE: functional biomarkers (cobalamin, methylmalonic acid, folate, α1 -proteinase inhibitor, immunoglobulin A), biochemical biomarkers (C-reactive protein, perinuclear anti-neutrophilic cytoplasmic antibodies, 3-bromotyrosine, N-methylhistamine, calprotectin, S100A12, soluble receptor of advanced glycation end products, cytokines and chemokines, alkaline phosphatase), microbiomic biomarkers (microbiome changes, dysbiosis index), metabolomic biomarkers (serum metabolome), genetic biomarkers (genomic markers, gene expression changes), and cellular biomarkers (regulatory T cells). In addition, important performance criteria of diagnostic tests are briefly reviewed.
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Affiliation(s)
- Romy M. Heilmann
- Small Animal ClinicCollege of Veterinary Medicine, University of LeipzigLeipzigSaxonyGermany
| | - Jörg M. Steiner
- Gastrointestinal LaboratoryCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationTX
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49
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Khanna R, Narula N, Feagan BG. The Role of Biomarkers in Clinical Trials of Inflammatory Bowel Disease. Inflamm Bowel Dis 2018; 24:1619-1623. [PMID: 29846593 DOI: 10.1093/ibd/izy195] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Indexed: 12/15/2022]
Abstract
Clinical trials require valid outcome measures to assess the therapeutic benefit of investigational agents. Recently, regulatory authorities have mandated the use of patient-reported outcomes in combination with an objective measure of disease activity as primary outcome measures in inflammatory bowel disease trials. Endoscopy has commonly fulfilled the latter role; however, due to the costs and complexity of these assessments, interest has emerged in the use of noninvasive biomarkers. The role of C-reactive protein, fecal calprotectin, and fecal lactoferrin in clinical research is discussed.
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Affiliation(s)
- Reena Khanna
- Department of Medicine, Division of Gastroenterology, University of Western Ontario, London, Ontario, Canada
| | - Neeraj Narula
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
| | - Brian G Feagan
- Department of Medicine, Division of Gastroenterology, University of Western Ontario, London, Ontario, Canada.,Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
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50
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Heida A, Van de Vijver E, van Ravenzwaaij D, Van Biervliet S, Hummel TZ, Yuksel Z, Gonera-de Jong G, Schulenberg R, Muller Kobold A, van Rheenen PF, the CACATU consortium. Predicting inflammatory bowel disease in children with abdominal pain and diarrhoea: calgranulin-C versus calprotectin stool tests. Arch Dis Child 2018; 103. [PMID: 29514815 PMCID: PMC5965359 DOI: 10.1136/archdischild-2017-314081] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
OBJECTIVE Calgranulin-C (S100A12) is a new faecal marker of inflammation that is potentially more specific for inflammatory bowel disease (IBD) than calprotectin, since it is only released by activated granulocytes. We compared calgranulin-C and calprotectin to see which of the two tests best predicted IBD in children with chronic abdominal pain and diarrhoea. DESIGN Delayed-type cross-sectional diagnostic study. SETTING AND PATIENTS Previously undiagnosed patients aged 6-17 years, who were seen in paediatric clinics in the Netherlands and Belgium, sent in a stool sample for analysis. Patients with a high likelihood of IBD underwent upper and lower endoscopy (ie, preferred reference test), while those with a low likelihood were followed for 6 months for latent IBD to become visible (ie, alternative reference test). We used Bayesian modelling to correct for differential verification bias. MAIN OUTCOME MEASURES Primary outcome was the specificity for IBD using predefined test thresholds (calgranulin-C: 0.75 µg/g, calprotectin: 50 µg/g). Secondary outcome was the test accuracy with thresholds based on receiver operating characteristics (ROC) analysis. RESULTS IBD was diagnosed in 93 of 337 patients. Calgranulin-C had significantly better specificity than calprotectin when predefined thresholds were used (97% (95% credible interval (CI) 94% to 99%) vs 71% (95% CI 63% to 79%), respectively). When ROC-based thresholds were used (calgranulin-C: 0.75 µg/g, calprotectin: 400 µg/g), both tests performed equally well (specificity: 97% (95% CI 94% to 99%) vs 98% (95% CI 95% to 100%)). CONCLUSIONS Both calgranulin-C and calprotectin have excellent test characteristics to predict IBD and justify endoscopy. TRIAL REGISTRATION NUMBER NCT02197780.
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Affiliation(s)
- Anke Heida
- Department of Paediatric Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Els Van de Vijver
- Department of Paediatric Gastroenterology, University Hospital Antwerp, Edegem, Belgium
| | - Don van Ravenzwaaij
- Department of Psychology, University of Groningen, Groningen, The Netherlands
| | | | - Thalia Z Hummel
- Department of Paediatrics, Medisch Spectrum Twente, Enschede, The Netherlands
| | - Zehre Yuksel
- Department of Paediatrics, Ziekenhuis Groep Twente, Almelo, The Netherlands
| | | | - Renate Schulenberg
- Department of Paediatrics, Ommelander Ziekenhuis Groningen, Winschoten, The Netherlands
| | - Anneke Muller Kobold
- Department of Laboratory Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Patrick Ferry van Rheenen
- Department of Paediatric Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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