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Shahub S, Kumar RM, Lin KC, Banga I, Choi NK, Garcia NM, Muthukumar S, Rubin DT, Prasad S. Continuous Monitoring of CRP, IL-6, and Calprotectin in Inflammatory Bowel Disease Using a Perspiration-Based Wearable Device. Inflamm Bowel Dis 2025; 31:647-654. [PMID: 38520737 DOI: 10.1093/ibd/izae054] [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: 10/13/2023] [Indexed: 03/25/2024]
Abstract
BACKGROUND Wearable sensor devices represent a noninvasive technology to continuously track biomarkers linked to inflammatory bowel disease (IBD). We assessed the inflammatory markers associated with IBD in human perspiration. METHODS Participants with IBD were monitored for 40 to 130 minutes with a proprietary wearable sensor device used to measure C-reactive protein, interleukin-6, and calprotectin. Sensor response using electrochemical impedance spectroscopy and serum samples were measured on the same day. The Mann-Whitney test was used to analyze the relationship between active and remission IBD in serum and perspiration, classified according to endoscopic reports and serum biomarker levels. Asynchronously collected fecal calprotectin from a subset of the population was similarly analyzed. RESULTS A total of 33 subjects were enrolled. Expression of calprotectin was significantly elevated in the active cohort compared with the remission cohort in perspiration (P < .05; median = 906.69 ng/mL; active 95% confidence interval [CI], 466.0-1833 ng/mL; remission 95% CI, 328.4-950.8 ng/mL), serum (median = 1860.82 ng/mL; active 95% CI, 1705-2985 ng/mL; remission 95% CI, 870.2-1786 ng/mL), and stool (P < .05; median = 126.74 µg/g; active 95% CI, 77.08-347.1 µg/g; remission 95% CI, 5.038-190.4 µg/g). Expression of CRP in perspiration and serum was comparable between the active and remission cohorts (perspiration: P > .05; median = 970.83 pg/mL; active 95% CI, 908.7-992 pg/mL; remission 95% CI, 903.3-991.9 pg/mL; serum: median = 2.34 µg/mL; active 95% CI, 1.267-4.492 µg/mL; remission 95% CI, 1.648-4.287 µg/mL). Expression of interleukin-6 in perspiration was nonsignificant in the active cohort compared with the remission cohort and was significantly elevated in serum (perspiration: P < .05; median = 2.13 pg/mL; active 95% CI, 2.124-2.44 pg/mL; remission 95% CI, 1.661-2.451 pg/mL; serum: median = 1.15 pg/mL; active 95% CI, 1.549-3.964 pg/mL; remission 95% CI, 0.4301-1.257 pg/mL). Analysis of the linear relationship between perspiration and serum calprotectin (R2 = 0.7195), C-reactive protein (R2 = 0.615), and interleukin-6 (R2 = 0.5411) demonstrated a strong to moderate relationship across mediums. CONCLUSIONS We demonstrate the clinical utility of perspiration as a noninvasive medium for continuous measurement of inflammatory markers in IBD and find that the measures correlate with serum and stool markers across a range of disease activity.
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Affiliation(s)
- Sarah Shahub
- Department of Bioengineering, University of Texas at Dallas, Dallas, TX, USA
| | | | - Kai-Chun Lin
- Department of Bioengineering, University of Texas at Dallas, Dallas, TX, USA
| | - Ivneet Banga
- Department of Bioengineering, University of Texas at Dallas, Dallas, TX, USA
| | - Natalie K Choi
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Nicole M Garcia
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | | | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Shalini Prasad
- Department of Bioengineering, University of Texas at Dallas, Dallas, TX, USA
- EnLiSense LLC, Allen, TX, United States
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Omar M, Omar M, Patt YS, Ukashi O, Sharif Y, Lahat A, Selinger CP, Sharif K. Genetic Risk of Ankylosing Spondylitis and Second-Line Therapy Need in Crohn's Disease: A Mendelian Randomization Study. J Clin Med 2024; 13:7496. [PMID: 39768419 PMCID: PMC11678710 DOI: 10.3390/jcm13247496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 12/02/2024] [Accepted: 12/08/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Crohn's disease (CD) and Ankylosing Spondylitis (AS) are chronic conditions with overlapping inflammatory pathways. This research investigates the genetic association between AS and the requirement for more aggressive therapeutic interventions in CD, suggesting a likelihood of increased severity in CD progression among individuals diagnosed with AS. Methods: This study utilized two-sample Mendelian randomization (TSMR) to analyze GWAS datasets for AS and CD requiring second-line treatment. Instrumental variables were selected based on single-nucleotide polymorphisms of genome-wide significance. Analytical methods included inverse-variance weighted (IVW), MR Egger, and other MR approaches, alongside sensitivity analysis, to validate the findings. Results: Our results indicated a significant association between AS genetic predisposition and the increased need for second-line treatments in CD. The IVW method showed an Odds Ratio (OR) of 2.16, and MR Egger provided an OR of 2.71, both were statistically significant. This association persisted even after the exclusion of influential outlier SNP rs2517655, confirming the robustness of our findings. Conclusions: This study suggests that genetic factors contributing to AS may influence the progression of CD, potentially necessitating more intensive treatment strategies. These findings underscore the importance of early screening in patients with co-existing AS and CD for tailoring treatment approaches, thus advancing personalized medicine in the management of these complex conditions.
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Affiliation(s)
- Mahmud Omar
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel;
| | - Mohammad Omar
- School of Medicine, V. N. Karazin Kharkiv National University, 61022 Kharkiv, Ukraine;
| | | | - Offir Ukashi
- Department of Gastroenterology, Sheba Medical Center, Tel-Hashomer 5262000, Israel; (O.U.); (A.L.)
| | - Yousra Sharif
- Department of Gastroenterology, Hadassah Medical Center, Jerusalem 91120, Israel;
| | - Adi Lahat
- Department of Gastroenterology, Sheba Medical Center, Tel-Hashomer 5262000, Israel; (O.U.); (A.L.)
| | | | - Kassem Sharif
- Internal Medicine B, Sheba Medical Centre, Ramat Gan 5262000, Israel;
- Department of Gastroenterology, Sheba Medical Center, Tel-Hashomer 5262000, Israel; (O.U.); (A.L.)
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals, Leeds LS1 3EX, UK
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De Avila J, Flórez-Sarmiento C, Parra-Izquierdo V, Bautista-Molano W, Chamorro-Melo M, Beltrán-Ostos A, Jaimes DA, Khoury V, Chila-Moreno L, Ramos-Casallas A, Bello-Gualtero JM, Gutiérrez J, Pacheco-Tena C, Chalem Choueka PS, Romero-Sánchez C. Elevated Calprotectin Levels Reveal Loss of Vascular Pattern and Atrophy of Villi in Ileum by Digital Chromoendoscopy and Magnification Colonoscopy in Patients with Spondyloarthritis Without Having Inflammatory Bowel Disease. Diagnostics (Basel) 2024; 14:2591. [PMID: 39594257 PMCID: PMC11593260 DOI: 10.3390/diagnostics14222591] [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: 07/10/2024] [Revised: 10/25/2024] [Accepted: 10/28/2024] [Indexed: 11/28/2024] Open
Abstract
OBJECTIVE This study aimed to establish a correlation between fecal calprotectin levels (FC) and intestinal inflammation in patients with spondyloarthritis without inflammatory bowel disease. METHODS A total of 180 SpA patients were included in the study of them 20.6% required Digital chromoendoscopy (DCE). FC, C-reactive protein (CRP), HLA-B*27 and clinical indices were assessed. RESULTS Positive fecal calprotectin (PFC) and high fecal calprotectin (HFC) levels were observed in 27.0% and 16.0% of patients, respectively. HFC correlated with a Bath Ankylosing Spondylitis Functional Index (BASFI) score > 4.0 (p = 0.036) and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score > 4.0 (p = 0.047). Loss of vascular pattern in the ileum (LVPI) was observed in approximately 70.0% of patients (p = 0.005), which was associated with PFC and abdominal bloating (p = 0.020). LVPI was also linked to microscopic inflammation (p = 0.012) and PFC with abdominal pain (p = 0.007). HFC was significantly associated with alterations in the ileal mucosa (p = 0.009) and LVPI (p = 0.001). Additionally, HFC and diarrhea were associated with LVPI in 27.3% of patients (p = 0.037) and with erosions in the ileum (p = 0.031). Chronic ileal inflammation correlated with HFC (p = 0.015), ASDAS-CRP > 2.1 (p = 0.09), LVPI (p = 0.001), and villous atrophy (p = 0.014). Factorial analysis of mixed data (FAMD) identified significant associations between micro/macroscopic changes in chronic inflammation and HFC (CC = 0.837); increased levels of CRP and microscopic acute inflammation (CC = 0.792); and clinical activity scores of ASDAS-CRP and BASDAI (CC = 0.914). CONLUSIONS FC levels were significantly elevated in patients with SpA, particularly those with LVPI, suggesting their potential as a valuable biomarker for managing SpA when joint manifestations coincide with ileal villous atrophy. This indicates a shared immune pathway linked to chronic gut damage.
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Affiliation(s)
- Juliette De Avila
- Cellular and Molecular Immunology Group–InmuBo, School of Dentistry, Universidad El Bosque, Av. Cra 9 No. 131 A–02, Bogotá 110121, Colombia; (J.D.A.); (C.F.-S.); (V.P.-I.); (W.B.-M.); (A.B.-O.); (L.C.-M.); (A.R.-C.)
| | - Cristian Flórez-Sarmiento
- Cellular and Molecular Immunology Group–InmuBo, School of Dentistry, Universidad El Bosque, Av. Cra 9 No. 131 A–02, Bogotá 110121, Colombia; (J.D.A.); (C.F.-S.); (V.P.-I.); (W.B.-M.); (A.B.-O.); (L.C.-M.); (A.R.-C.)
- Gastroadvanced, Bogotá 110221, Colombia
| | - Viviana Parra-Izquierdo
- Cellular and Molecular Immunology Group–InmuBo, School of Dentistry, Universidad El Bosque, Av. Cra 9 No. 131 A–02, Bogotá 110121, Colombia; (J.D.A.); (C.F.-S.); (V.P.-I.); (W.B.-M.); (A.B.-O.); (L.C.-M.); (A.R.-C.)
- Gastroadvanced, Bogotá 110221, Colombia
| | - Wilson Bautista-Molano
- Cellular and Molecular Immunology Group–InmuBo, School of Dentistry, Universidad El Bosque, Av. Cra 9 No. 131 A–02, Bogotá 110121, Colombia; (J.D.A.); (C.F.-S.); (V.P.-I.); (W.B.-M.); (A.B.-O.); (L.C.-M.); (A.R.-C.)
- Clinical Immunology Group, Rheumatology and Immunology Department, School of Medicine, Hospital Militar Central, Universidad Militar Nueva Granada, Transversal 3ª # 49-00, Bogotá 110231, Colombia; (M.C.-M.); (J.M.B.-G.); (J.G.)
| | - Magaly Chamorro-Melo
- Clinical Immunology Group, Rheumatology and Immunology Department, School of Medicine, Hospital Militar Central, Universidad Militar Nueva Granada, Transversal 3ª # 49-00, Bogotá 110231, Colombia; (M.C.-M.); (J.M.B.-G.); (J.G.)
| | - Adriana Beltrán-Ostos
- Cellular and Molecular Immunology Group–InmuBo, School of Dentistry, Universidad El Bosque, Av. Cra 9 No. 131 A–02, Bogotá 110121, Colombia; (J.D.A.); (C.F.-S.); (V.P.-I.); (W.B.-M.); (A.B.-O.); (L.C.-M.); (A.R.-C.)
| | | | - Valery Khoury
- School of Medicine, Universidad El Bosque, Bogotá 110121, Colombia;
| | - Lorena Chila-Moreno
- Cellular and Molecular Immunology Group–InmuBo, School of Dentistry, Universidad El Bosque, Av. Cra 9 No. 131 A–02, Bogotá 110121, Colombia; (J.D.A.); (C.F.-S.); (V.P.-I.); (W.B.-M.); (A.B.-O.); (L.C.-M.); (A.R.-C.)
| | - Alejandro Ramos-Casallas
- Cellular and Molecular Immunology Group–InmuBo, School of Dentistry, Universidad El Bosque, Av. Cra 9 No. 131 A–02, Bogotá 110121, Colombia; (J.D.A.); (C.F.-S.); (V.P.-I.); (W.B.-M.); (A.B.-O.); (L.C.-M.); (A.R.-C.)
| | - Juan Manuel Bello-Gualtero
- Clinical Immunology Group, Rheumatology and Immunology Department, School of Medicine, Hospital Militar Central, Universidad Militar Nueva Granada, Transversal 3ª # 49-00, Bogotá 110231, Colombia; (M.C.-M.); (J.M.B.-G.); (J.G.)
| | - Jaiber Gutiérrez
- Clinical Immunology Group, Rheumatology and Immunology Department, School of Medicine, Hospital Militar Central, Universidad Militar Nueva Granada, Transversal 3ª # 49-00, Bogotá 110231, Colombia; (M.C.-M.); (J.M.B.-G.); (J.G.)
| | | | | | - Consuelo Romero-Sánchez
- Cellular and Molecular Immunology Group–InmuBo, School of Dentistry, Universidad El Bosque, Av. Cra 9 No. 131 A–02, Bogotá 110121, Colombia; (J.D.A.); (C.F.-S.); (V.P.-I.); (W.B.-M.); (A.B.-O.); (L.C.-M.); (A.R.-C.)
- Clinical Immunology Group, Rheumatology and Immunology Department, School of Medicine, Hospital Militar Central, Universidad Militar Nueva Granada, Transversal 3ª # 49-00, Bogotá 110231, Colombia; (M.C.-M.); (J.M.B.-G.); (J.G.)
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Luo X, Li J, Yang M, Tu L, Xie Y, Lv Q, Wen S, Wen X, Zhou L, Gu J. Alterations in peripheral T-cell and B-cell subsets in the ankylosing spondylitis patients with gut inflammation. Int J Rheum Dis 2024; 27:e15324. [PMID: 39380421 DOI: 10.1111/1756-185x.15324] [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: 02/20/2024] [Revised: 08/08/2024] [Accepted: 08/15/2024] [Indexed: 10/10/2024]
Abstract
AIM This study investigates changes in immune cell subsets in peripheral blood of ankylosing spondylitis (AS) patients with colitis or terminal ileitis. It aims to explore the connection between changes in lymphocyte subsets and gut inflammation, providing insights for early detection. METHODS Overall, 50 AS patients undergoing colonoscopy were enrolled. Flow cytometry was employed to analyze lymphocyte subsets, including T and B cells, in peripheral blood. Disease activity was assessed using CRP, ESR, BASDAI, ASDAS-CRP, and ASDAS-ESR. RESULTS Compared to AS patients without gut inflammation, those with colorectal inflammation showed a significant increase in total T cells (p < .05), an increase in exhausted CD4+ T cells (p < .05), and a decrease in Th2 cells and total Tc cells (p < .05). Notably, in AS patients with terminal ileitis, there was an increase in total B cells and classic switched B cells (p < .05), with a decrease in double-positive T cells (p < .05). However, no significant differences were observed in the distribution of Tfh-cell subpopulations (Tfh1, Tfh2, Tfh17) and Tc-cell subpopulations (Tc1, Tc2, Tc17) between AS patients with either colorectal inflammation or terminal ileitis (p > .05). We explored the relationship between disease activity scores, ESR, CRP, and lymphocyte subsets, but found no statistically significant correlation between them. CONCLUSION Distinct immune patterns may exist in AS with different types of intestinal inflammation. Colitis in AS is primarily characterized by a significant increase in exhausted CD4+ T cells, along with a decrease in Th2 cells. In contrast, terminal ileum inflammation in AS is marked by an increase in total B cells and classic switched B cells. These findings offer new insights for early detection and therapeutic intervention.
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Affiliation(s)
- Xiqing Luo
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jinwei Li
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Mingcan Yang
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Liudan Tu
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ya Xie
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qing Lv
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Shenghui Wen
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Xianghui Wen
- Shenzhen Institute of Immunomedicine Transformation (Longhua), Shenzhen, China
| | - Liuzhong Zhou
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jieruo Gu
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Ondrejčáková L, Gregová M, Bubová K, Šenolt L, Pavelka K. Serum biomarkers and their relationship to axial spondyloarthritis associated with inflammatory bowel diseases. Autoimmun Rev 2024; 23:103512. [PMID: 38168574 DOI: 10.1016/j.autrev.2023.103512] [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: 12/15/2023] [Accepted: 12/29/2023] [Indexed: 01/05/2024]
Abstract
Spondyloarthritis (SpA) constitute a group of chronic inflammatory immune-mediated rheumatic diseases characterized by genetic, clinical, and radiological features. Recent efforts have concentrated on identifying biomarkers linked to axial SpA associated with inflammatory bowel disease (IBD), offering predictive insights into disease onset, activity, and progression. Genetically, the significance of the HLA-B27 antigen is notably diminished in ankylosing spondylitis (AS) associated with IBD, but is heightened in concurrent sacroiliitis. Similarly, certain polymorphisms of endoplasmic reticulum aminopeptidase (ERAP-1) appear to be involved. Carriage of variant NOD2/CARD15 polymorphisms has been demonstrated to correlate with the risk of subclinical intestinal inflammation in AS. Biomarkers indicative of pro-inflammatory activity, including C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR), are among the consistent predictive biomarkers of disease progression. Nevertheless, these markers are not without limitations and exhibit relatively low sensitivity. Other promising markers encompass IL-6, serum calprotectin (s-CLP), serum amyloid (SAA), as well as biomarkers regulating bone formation such as metalloproteinase-3 (MMP-3) and Dickkopf-related protein 1 (DKK-1). Additional candidate indicators of structural changes in SpA patients include matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF), tenascin C (TNC), and CD74 IgG. Fecal caprotein (f-CLP) levels over long-term follow-up of AS patients have demonstrated predictive value in anticipating the development of IBD. Serologic antibodies characteristic of IBD (ASCA, ANCA) have also been compared; however, results exhibit variability. In this review, we will focus on biomarkers associated with both axial SpA and idiopathic intestinal inflammation, notably enteropathic spondyloarthritis.
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Affiliation(s)
- L Ondrejčáková
- Institute of Rheumatology, Prague, Czech Republic; Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - M Gregová
- Institute of Rheumatology, Prague, Czech Republic; Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - K Bubová
- Institute of Rheumatology, Prague, Czech Republic; Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
| | - L Šenolt
- Institute of Rheumatology, Prague, Czech Republic; Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
| | - K Pavelka
- Institute of Rheumatology, Prague, Czech Republic; Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
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Mazeda C, Silva SP, Pinto Oliveira C, Azevedo S, Barcelos A. GIScaSpA-study of subclinical gut involvement in axial spondyloarthritis. Rheumatol Adv Pract 2024; 8:rkae016. [PMID: 38414917 PMCID: PMC10898325 DOI: 10.1093/rap/rkae016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/19/2024] [Indexed: 02/29/2024] Open
Affiliation(s)
- Carolina Mazeda
- Rheumatology Department, Centro Hospitalar do Baixo Vouga, Aveiro, Portugal
- Centro Académico Clínico Egas Moniz, Health Alliance, Aveiro, Portugal
- EpiDoc Unit, Nova Medical School, NOVA University Lisbon, Lisbon, Portugal
| | - Susana P Silva
- Rheumatology Department, Centro Hospitalar do Baixo Vouga, Aveiro, Portugal
- Centro Académico Clínico Egas Moniz, Health Alliance, Aveiro, Portugal
| | - C Pinto Oliveira
- Rheumatology Department, Centro Hospitalar do Baixo Vouga, Aveiro, Portugal
- Centro Académico Clínico Egas Moniz, Health Alliance, Aveiro, Portugal
| | - Sofia Azevedo
- Rheumatology Department, Centro Hospitalar do Baixo Vouga, Aveiro, Portugal
- Centro Académico Clínico Egas Moniz, Health Alliance, Aveiro, Portugal
| | - Anabela Barcelos
- Rheumatology Department, Centro Hospitalar do Baixo Vouga, Aveiro, Portugal
- Centro Académico Clínico Egas Moniz, Health Alliance, Aveiro, Portugal
- EpiDoc Unit, Nova Medical School, NOVA University Lisbon, Lisbon, Portugal
- Comprehensive Health Research Center, Universidade NOVA de Lisboa, Lisbon, Portugal
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Bernard J, Barnetche T, Amory C, Despres J, Vandersmissen M, Landrin J, Gaujoux-Viala C, Lukas C, Ruyssen-Witrand A, Truchetet ME, Vergne-Salle P, Mathieu S, Tournadre A. Frequency of irritable bowel syndrome in spondyloarthritis: a multicentric cross-sectional study and meta-analysis. RMD Open 2024; 10:e003836. [PMID: 38216286 PMCID: PMC10806458 DOI: 10.1136/rmdopen-2023-003836] [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: 10/21/2023] [Accepted: 12/19/2023] [Indexed: 01/14/2024] Open
Abstract
OBJECTIVE To evaluate the prevalence of symptoms and factors associated with irritable bowel syndrome (IBS) in axial spondyloarthritis (ax-SpA). METHODS In a cross-sectional multicentric study, consecutive patients with ax-SpA treated with biologics in five rheumatology departments were asked for IBS Rome IV criteria. Demographic data, lifestyle behaviours and disease characteristics were recorded. Second, a systematic literature review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS Of the 500 patients with ax-SpA included, 124 reported IBS symptoms (25%). Female gender, unemployment, higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and worse Bath Ankylosing Spondylitis Functional Index scores, multiple lines of biologics, fibromyalgia, anxiety, depression and lower physical activity were associated with IBS symptoms. In multivariate model, the risk of IBS was associated with anxiety and physical inactivity. From the literature review, the prevalence of IBS in patients with SpA was 15.4% (8.8% to 23.3%). Meta-analysis of the five studies comparing the presence of IBS in patients with SpA (323/7292) and healthy controls (484/35587) showed a significant increase of IBS in patients with SpA (OR=1.59 (1.05 to 2.40)). CONCLUSION The prevalence of IBS symptoms was high in the ax-SpA population and should therefore be considered in the presence of gastrointestinal disorders. The presence of IBS symptoms was associated with anxiety and low physical activity in multivariate analysis. Patients with IBS symptoms tended to have more difficult to manage disease characterised by higher activity, worse functional score and multiple lines of treatment in univariate analysis.
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Affiliation(s)
- Jessika Bernard
- Rheumatology, Clermont-Ferrand University Hospital, Rheumatology Department, UNH-UMR 1019, INRAe and University Clermont Auvergne, Clermont-Ferrand, France
| | - Thomas Barnetche
- Rheumatology, Bordeaux University Hospital FHU ACRONIM, Bordeaux, France
| | - Charlotte Amory
- Rheumatology, University Hospital Lapeyronie, Montpellier, France
| | - Jerome Despres
- Rheumatology, Toulouse University Hospital, Rheumatology Centre, Centre d'Investigation Clinique de Toulouse CIC1436, Inserm, Team PEPSS « Pharmacologie En Population cohorteS et biobanqueS » University of Toulouse 3, Toulouse, France
| | - Maxime Vandersmissen
- Rheumatology, Limoges University Hospital, team CAPtuR, UMR Inserm 1308, University of Limoges, France, Limoges, France
| | - Justine Landrin
- Rheumatology, Bordeaux University Hospital FHU ACRONIM, Bordeaux, France
| | - Cecile Gaujoux-Viala
- Rheumatology, Nîmes University Hospital, Nîmes, France
- UA11 Institut Desbrest d'Épidémiologie et de Santé Publique, University of Montpellier, INSERM, Montpellier, France
| | - Cédric Lukas
- Rheumatology, University Hospital Lapeyronie, Montpellier, France
- UA11 Institut Desbrest d'Épidémiologie et de Santé Publique, University of Montpellier, INSERM, Montpellier, France
| | - Adeline Ruyssen-Witrand
- Rheumatology, Toulouse University Hospital, Rheumatology Centre, Centre d'Investigation Clinique de Toulouse CIC1436, Inserm, Team PEPSS « Pharmacologie En Population cohorteS et biobanqueS » University of Toulouse 3, Toulouse, France
| | | | - Pascale Vergne-Salle
- Rheumatology, Limoges University Hospital, team CAPtuR, UMR Inserm 1308, University of Limoges, France, Limoges, France
| | - Sylvain Mathieu
- Rheumatology, Clermont-Ferrand University Hospital, Rheumatology Department, UNH-UMR 1019, INRAe and University Clermont Auvergne, Clermont-Ferrand, France
| | - Anne Tournadre
- Rheumatology, Clermont-Ferrand University Hospital, Rheumatology Department, UNH-UMR 1019, INRAe and University Clermont Auvergne, Clermont-Ferrand, France
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Carubbi F, Alunno A, Viscido A, Baraliakos X, Mariani FM, Di Ruscio E, Altieri P, Ferri C. SpA plus IBD or IBD plus SpA: Does commutative property apply? Autoimmun Rev 2023; 22:103443. [PMID: 37678619 DOI: 10.1016/j.autrev.2023.103443] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 09/03/2023] [Indexed: 09/09/2023]
Abstract
The term spondyloarthritis (SpA) encompasses a group of interrelated disorders characterised by the involvement of the musculoskeletal system as well as extra-articular manifestations like acute anterior uveitis, psoriasis and inflammatory bowel diseases (IBD). Likewise, IBD may present with various extra-intestinal manifestations among which those involving the musculoskeletal system, namely peripheral and axial SpA are the most common. The identification of patients with both SpA and IBD is of paramount importance in clinical practice since the coexistence of these two entities has been associated with great disability and decreased quality of life. In order to achieve an early diagnosis of IBD-SpA it is instrumental that rheumatologists seek for gastrointestinal symptoms in SpA patients and likewise that gastroenterologists seek for inflammatory musculoskeletal symptoms in patients with IBD. This narrative review aims at critically appraising the available evidence about SpA occurring in IBD patients versus IBD occurring in patients with SpA and at highlighting similarities and differences between the two scenarios.
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Affiliation(s)
- Francesco Carubbi
- University of L'Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, Internal Medicine and Nephrology Division, ASL 1 Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy.
| | - Alessia Alunno
- University of L'Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, Internal Medicine and Nephrology Division, ASL 1 Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy
| | - Angelo Viscido
- University of L'Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, Internal Medicine and Nephrology Division, ASL 1 Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy
| | | | - Francesco Maria Mariani
- University of L'Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, Internal Medicine and Nephrology Division, ASL 1 Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy
| | - Evy Di Ruscio
- University of L'Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, Internal Medicine and Nephrology Division, ASL 1 Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy
| | - Piera Altieri
- University of L'Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, Internal Medicine and Nephrology Division, ASL 1 Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy
| | - Claudio Ferri
- University of L'Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, Internal Medicine and Nephrology Division, ASL 1 Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy
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9
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Tung KK, Chen ST, Lee CH, Tung CF, Wei JCC. Calprotectin in spondyloarthritis and gut inflammation, is it clinically meaningful? Int J Rheum Dis 2023; 26:609-612. [PMID: 37002903 DOI: 10.1111/1756-185x.14619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 01/18/2023] [Accepted: 02/06/2023] [Indexed: 04/04/2023]
Affiliation(s)
- Kuan-Kai Tung
- Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Shih-Tien Chen
- Department of Gastroenterology and Hepatology, Chia-Yi Hospital, Ministry of Health and Welfare, Chiayi, Taiwan
| | - Cheng-Hung Lee
- Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan
- Post Baccalaureate Medicine, School of Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Food Science and Technology, Hung Kuang University, Taichung, Taiwan
| | - Chun-Fang Tung
- Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, National Yang-Ming Chao-Tung University, Taipei, Taiwan
| | - James Cheng-Chung Wei
- Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
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10
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Turpin W, Lee SH, Croitoru K. Reply. Gastroenterology 2023; 164:501-502. [PMID: 36379245 DOI: 10.1053/j.gastro.2022.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 11/01/2022] [Indexed: 11/15/2022]
Affiliation(s)
- Williams Turpin
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Sun-Ho Lee
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Kenneth Croitoru
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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11
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Parthasarathy R, Santiago F, McCluskey P, Kaakoush NO, Tedla N, Wakefield D. The microbiome in HLA-B27-associated disease: implications for acute anterior uveitis and recommendations for future studies. Trends Microbiol 2023; 31:142-158. [PMID: 36058784 DOI: 10.1016/j.tim.2022.08.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 08/09/2022] [Accepted: 08/09/2022] [Indexed: 01/27/2023]
Abstract
The pathogenesis of human leukocyte antigen (HLA)-B27-associated diseases such as acute anterior uveitis (AAU) and ankylosing spondylitis (AS) remains poorly understood, though Gram-negative bacteria and subclinical bowel inflammation are strongly implicated. Accumulating evidence from animal models and clinical studies supports several hypotheses, including HLA-B27-dependent dysbiosis, altered intestinal permeability, and molecular mimicry. However, the existing literature is hampered by inadequate studies designed to establish causation or uncover the role of viruses and fungi. Moreover, the unique disease model afforded by AAU to study the gut microbiota has been neglected. This review critically evaluates the current literature and prevailing hypotheses on the link between the gut microbiota and HLA-B27-associated disease. We propose a new potential role for HLA-B27-driven altered antibody responses to gut microbiota in disease pathogenesis and outline recommendations for future well-controlled human studies, focusing on AAU.
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Affiliation(s)
- Rohit Parthasarathy
- School of Medical Sciences, Faculty of Medicine & Health, UNSW, Sydney, Australia
| | - Fernando Santiago
- School of Medical Sciences, Faculty of Medicine & Health, UNSW, Sydney, Australia
| | - Peter McCluskey
- Save Sight Institute, Sydney Eye Hospital, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Nadeem O Kaakoush
- School of Medical Sciences, Faculty of Medicine & Health, UNSW, Sydney, Australia
| | - Nicodemus Tedla
- School of Medical Sciences, Faculty of Medicine & Health, UNSW, Sydney, Australia
| | - Denis Wakefield
- School of Medical Sciences, Faculty of Medicine & Health, UNSW, Sydney, Australia; Center for Immunology and Immunopathology, South Eastern Area Health Service, Sydney, Australia.
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12
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Huang R, Zhang M, Lu Y, Xu D, Liu Y, Jin M, Xian S, Wang S, Tong X, Lu J, Zhang W, Qian W, Tang J, Yang Y, Lu B, Chang Z, Liu X, Ji S. Effects of intestinal microbes on rheumatic diseases: A bibliometric analysis. Front Microbiol 2023; 13:1074003. [PMID: 36699603 PMCID: PMC9870327 DOI: 10.3389/fmicb.2022.1074003] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 12/05/2022] [Indexed: 01/12/2023] Open
Abstract
Background Rheumatic diseases (RD) are a group of multi-system inflammatory autoimmune diseases whose causes are still under study. In the past few decades, researchers have found traces of the association between rheumatic diseases and intestinal microbiota, which can partially explain the pathogenesis of rheumatic diseases. We aimed to describe the research trend and main divisions on how gut flora interreacts with rheumatic diseases, and discussed about the possible clinical applications. Methods We analyzed bibliometric data from the Web of Science core collection (dated 15th May 2022). Biblioshiny R language software packages (bibliometrix) were used to obtain the annual publication and citations, core sources according to Bradford's law, and country collaboration map. We designed and verified the keyword co-occurrence network and strategic diagram with the help of VOSviewer and CiteSpace, subdivided the research topic into several themes and identified research dimensions. The tables of most local cited documents and core sources were processed manually. Furthermore, the Altmetric Attention Score and the annual Altmetric Top 100 were applied to analyze the annual publication and citation. Results From a total of 541 documents, we found that the overall trend of annual publication and citation is increasing. The major research method is to compare the intestinal microbial composition of patients with certain rheumatic disease and that of the control group to determine microbial alterations related to the disease's occurrence and development. According to Bradford's law, the core sources are Arthritis and Rheumatology, Annals of the Rheumatic Diseases, Current Opinion in Rheumatology, Nutrients, Rheumatology, and Journal of Rheumatology. Since 1976, 101 countries or regions have participated in studies of rheumatology and intestinal microbes. The United States ranks at the top and has the broadest academic association with other countries. Five themes were identified, including the pivotal role of inflammation caused by intestinal bacteria in the rheumatic pathogenesis, the close relationship between rheumatic diseases and inflammatory bowel disease, immunoregulation mechanism as a mediator of the interaction between rheumatic diseases and gut flora, dysbiosis and decreased diversity in intestine of patients with rheumatic diseases, and the influence of oral flora on rheumatic diseases. Additionally, four research dimensions were identified, including pathology, treatment, disease, and experiments. Conclusion Studies on rheumatic diseases and the intestinal microbiota are growing. Attention should be paid to the mechanism of their interaction, such as the microbe-immune-RD crosstalk. Hopefully, the research achievements can be applied to diseases' prevention, diagnosis, and treatment, and our work can contribute to the readers' future research.
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Affiliation(s)
- Runzhi Huang
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Shanghai, China
| | - Mengyi Zhang
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yuwei Lu
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Dayuan Xu
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Shanghai, China
| | - Yifan Liu
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Minghao Jin
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Shuyuan Xian
- School of Medicine, Tongji University, Shanghai, China
| | - Siqiao Wang
- School of Medicine, Tongji University, Shanghai, China
| | - Xirui Tong
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Shanghai, China
| | - Jianyu Lu
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Shanghai, China
| | - Wei Zhang
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Shanghai, China
| | - Weijin Qian
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jieling Tang
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yiting Yang
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Bingnan Lu
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhengyan Chang
- Department of Pathology, School of Medicine, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China,*Correspondence: Zhengyan Chang,
| | - Xin Liu
- Department of Rheumatology and Immunology, Second Affiliated Hospital of Naval Medical University, Shanghai, China,Xin Liu,
| | - Shizhao Ji
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Shanghai, China,Shizhao Ji,
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13
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Decreased fecal calprotectin levels in Spondyloarthritis patients colonized by Blastocystis spp. Sci Rep 2022; 12:15840. [PMID: 36151228 PMCID: PMC9508226 DOI: 10.1038/s41598-022-18308-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 08/09/2022] [Indexed: 11/08/2022] Open
Abstract
Spondyloarthritis (SpA) is a group of chronic inflammatory systemic diseases mainly characterized by inflammation in the spine and/or peripheral joints. Although a link between SpA-pathogenesis, intestinal inflammation and gut dysbiosis has been proposed, studies have been focused on bacteria-host interactions and very little has been reported regarding intestinal parasites. Here, intestinal parasitic infection of 51 SpA-patients were evaluated and compared to healthy control individuals. No significant differences in the frequency of any parasite between SpA-patients and control individuals were found. Significantly higher levels of fecal calprotectin (FCP) were found in the SpA-patients compared to the control individuals. However, FCP levels were the same when comparing SpA-patients and control individuals, both colonized by Blastocystis spp. On the other hand, when comparing Blastocystis spp. colonized and Blastocystis spp. free SpA-patients, FCP levels were significantly higher in those Blastocystis spp. free. Without ignoring the small sample size as a study limitation, the results showed that in the SpA-patients colonized by Blastocystis spp., the FCP levels were significantly lower than those in the Blastocystis spp. free group and comparable to those in the control group. These findings seem to suggest a relationship between Blastocystis spp. and intestinal inflammation in SpA-patients, but studies intended to explore that interaction specifically should be designed.
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14
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Campos JF, Resende GG, Barbosa AJA, de Carvalho SC, Lage JA, Cunha PFS, de Souza SCS, Ferrari MDLA. Fecal calprotectin as a biomarker of microscopic bowel inflammation in patients with spondyloarthritis. Int J Rheum Dis 2022; 25:1078-1086. [PMID: 35855677 DOI: 10.1111/1756-185x.14388] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 06/02/2022] [Accepted: 06/26/2022] [Indexed: 11/27/2022]
Abstract
AIM Microscopic bowel inflammation is present in up to 60% of all patients with spondyloarthritis (SpA) and appears to be associated with more severe joint disease and a higher risk of developing inflammatory bowel disease (IBD). This study aimed to determine the utility of fecal calprotectin (fCAL) in evaluating endoscopic and histological bowel inflammation in SpA patients. METHODS Ileocolonoscopies with biopsies and fCAL measurements were performed in 65 patients with SpA. RESULTS In 47 (72.3%) patients, the fCAL levels were higher than 50 μg/g, whereas in 20 (30.7%), these levels were greater than 250 μg/g. A total of 38 (58.5%) patients presented with microscopic bowel inflammation, and 13 (20%) presented with signs of endoscopic inflammation. fCAL levels were significantly higher in patients with microscopic bowel inflammation than in those without inflammatory findings (P < .001); additionally, these levels were slightly higher in patients with endoscopic signs of bowel inflammation (P = .053). A fCAL cutoff value of 96 μg/g predicted histological bowel inflammation with 73% sensitivity and 67% specificity. No statistically significant difference was observed in the fCAL levels between patients who had been treated or not treated with nonsteroidal anti-inflammatory drugs (NSAIDs). CONCLUSION Our findings confirm a high prevalence of microscopic bowel inflammation in SpA patients, regardless of the use of NSAIDs. The evaluation of fCAL levels proved to be useful in the identification of microscopic inflammation and could help in the more judicious indication of ileocolonoscopy. These results support the use of fCAL for the evaluation of microscopic bowel inflammation in SpA patients.
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Affiliation(s)
- Júlia Faria Campos
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Gustavo Gomes Resende
- Departamento de Reumatologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Alfredo José Afonso Barbosa
- Departamento de Patologia Clínica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Silas Castro de Carvalho
- Departamento de Endoscopia Digestiva, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Junia Aguiar Lage
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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15
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Expression of CD44 in Leukocyte Subpopulations in Patients with Inflammatory Bowel Diseases. Diagnostics (Basel) 2022; 12:diagnostics12082014. [PMID: 36010364 PMCID: PMC9407096 DOI: 10.3390/diagnostics12082014] [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: 07/20/2022] [Revised: 08/17/2022] [Accepted: 08/18/2022] [Indexed: 11/17/2022] Open
Abstract
CD44 expressed in monocytes and lymphocytes seems to play a crucial role in gastrointestinal inflammation, such as the one occurring in the context of inflammatory bowel diseases. Differentially methylated genes are distinctly expressed across monocyte subpopulations related to the state of Crohn’s disease. Hence, the aim of this study was to detect CD44 expression in leukocyte subpopulations in relation to the type of IBD, therapy, and disease duration. Monocyte subpopulations CD14++CD16−, CD14++CD16++, and CD14+CD16+ as well as other leukocytes were analyzed for their CD44 expression using flow cytometry in 46 patients with IBD and 48 healthy controls. Patients with Crohn’s disease treated with non-biological therapy (NBT) exhibited a lower percentage of anti-inflammatory CD14+CD16++ monocytes, whereas NBT-treated patients with ulcerative colitis had lower expression of CD44 on CD14+CD44+ lymphocytes in comparison to controls, respectively. Conversely, patients with Crohn’s disease treated with biological therapy had a higher percentage of CD44+ granulocytes but lower expression of CD44 on anti-inflammatory monocytes compared to controls. Median fluorescence intensity (MFI) of CD44 on CD44+CD14+ lymphocytes was higher in ulcerative colitis patients treated with biological therapy compared to NBT. The percentage of classical CD14++CD16− monocytes was lower in the <9 years of IBD duration subgroup compared with the longer disease duration subgroup. The present study addresses the putative role of differentiation and regulation of leukocytes in tailoring IBD therapeutic regimes.
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16
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Wang L, Song C, Wang Y, Hu L, Liu X, Zhang J, Ji X, Man S, Zhang N, Li G, Yang Y, Peng L, Wei Z, Huang F. Symptoms Compatible with Rome IV Functional Bowel Disorder in Patients with Ankylosing Spondylitis. Mod Rheumatol 2022:6612220. [PMID: 35727178 DOI: 10.1093/mr/roac064] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 03/21/2022] [Accepted: 06/20/2022] [Indexed: 11/14/2022]
Abstract
OBJECTIVES To determine the frequency of symptoms meeting Rome IV functional bowel disorder (FBD) in patients with ankylosing spondylitis (AS), investigate factors associated with FBD symptoms, and assess whether having FBD symptoms might influence AS disease activity. METHODS In this cross-sectional study, we enrolled 153 AS patients without known colonic ulcer and 56 sex- and age-matched controls to evaluate FBD (or its subtypes) symptoms. Disease characteristics were also evaluated in AS group. RESULTS Sixty (39.2%) of 153 AS patients had FBD symptoms, which was more prevalent than controls (23.2%). Besides, symptoms compatible with irritable bowel syndrome (IBS) and chronic diarrhea were detected in 18 and 43 AS patients respectively. For AS group, multivariable logistic regression analyses showed that symptoms of FBD, IBS, and chronic diarrhea were negatively associated with using non-steroidal anti-inflammatory drug (NSAID), and positively associated with comorbid fibromyalgia, respectively. In exploration about effects of FBD (or its subtypes) symptoms on AS disease activity by multivariable linear regression analyses, FBD symptoms and chronic diarrhea had universal positive associations with assessments of AS disease characteristics respectively. CONCLUSION Patients with AS had frequent symptoms compatible with FBD, IBS, and chronic diarrhea, proportions of which were lower in those with NSAID-use. The improvement of FBD symptoms and chronic diarrhea might be conducive to disease status of AS patients.
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Affiliation(s)
- Lei Wang
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.,Medical School of Chinese PLA, Beijing, China
| | - Chuan Song
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.,Medical School of Chinese PLA, Beijing, China
| | - Yiwen Wang
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lidong Hu
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xingkang Liu
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Jiaxin Zhang
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.,Medical School of Chinese PLA, Beijing, China
| | - Xiaojian Ji
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Siliang Man
- Department of Rheumatology, Beijing JiShuiTan Hospital, Beijing, China
| | - Nana Zhang
- Medical School of Chinese PLA, Beijing, China.,Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Gang Li
- Health Service Department of the Guard Bureau of the Joint Staff Department, Beijing, China
| | - Yunsheng Yang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lihua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Zhimin Wei
- Health Service Department of the Guard Bureau of the Joint Staff Department, Beijing, China
| | - Feng Huang
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
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17
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Sagard J, Olofsson T, Mogard E, Marsal J, Andréasson K, Geijer M, Kristensen LE, Lindqvist E, Wallman JK. Gut dysbiosis associated with worse disease activity and physical function in axial spondyloarthritis. Arthritis Res Ther 2022; 24:42. [PMID: 35151357 PMCID: PMC8840679 DOI: 10.1186/s13075-022-02733-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 01/31/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Based on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut dysbiosis, intrinsic to IBD, has also been observed in axSpA. It is, however, not established to what degree gut dysbiosis is associated with axSpA disease severity. The objective of this study was to compare gut dysbiosis frequency between controls, non-radiographic axial spondyloarthritis (nr-axSpA), and ankylosing spondylitis (AS) patients and investigate whether gut dysbiosis is cross-sectionally associated with axSpA disease activity, physical function, mobility, or pain. METHODS Gut dysbiosis was assessed by 16SrRNA analysis of feces from 44/88 nr-axSpA/AS patients (ASAS/mNY criteria) without inflammatory bowel disease (IBD) and 46 controls without IBD or rheumatic disease. The GA-map™ Dysbiosis Test was used, grading gut microbiota aberrations on a 1-5 scale, where ≥3 denotes dysbiosis. Proportions with dysbiosis were compared between the groups. Furthermore, standard axSpA measures of disease activity, function, mobility, and pain were compared between patients (nr-axSpA and AS combined) with and without dysbiosis, univariately, and adjusted for relevant confounders (ANCOVA). RESULTS Gut dysbiosis was more frequent in AS than controls (36% versus 17%, p=0.023), while nr-axSpA (25% dysbiosis) did not differ significantly from either AS or controls. Univariately, most axSpA measures were significantly worse in patients with dysbiosis versus those without: ASDAS-CRP between-group difference 0.6 (95% CI 0.2-0.9); BASDAI 1.6 (0.8-2.4); evaluator's global disease activity assessment (Likert scale 0-4) 0.3 (0.1-0.5), BASFI 1.5 (0.6-2.4), and VAS pain (cm) 1.3 (0.4-2.2). Differences remained significant after adjustment for demographics, lifestyle factors, treatments, gut inflammation (fecal calprotectin ≥50 mg/kg), and gut symptoms, except for VAS pain. BASMI and CRP were not associated with dysbiosis. CONCLUSION Gut dysbiosis, more frequent in AS patients than controls, is associated with worse axSpA disease activity and physical function, seemingly irrespective of both gut inflammation and treatments. This provides further evidence for an important link between disturbances in gastrointestinal homeostasis and axSpA.
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Affiliation(s)
- Jonas Sagard
- Section of Rheumatology, Department of Clinical Sciences Lund, Lund University, Kioskgatan 5, 22185, Lund, Sweden.
- Skåne University Hospital, Department of Rheumatology, Lund, Sweden.
| | - Tor Olofsson
- Section of Rheumatology, Department of Clinical Sciences Lund, Lund University, Kioskgatan 5, 22185, Lund, Sweden
- Skåne University Hospital, Department of Rheumatology, Lund, Sweden
| | - Elisabeth Mogard
- Section of Rheumatology, Department of Clinical Sciences Lund, Lund University, Kioskgatan 5, 22185, Lund, Sweden
- Skåne University Hospital, Department of Rheumatology, Lund, Sweden
| | - Jan Marsal
- Department of Immunology, EMV, Lund University, Lund, Sweden
- Department of Gastroenterology, Skåne University Hospital, Lund/Malmö, Sweden
| | - Kristofer Andréasson
- Section of Rheumatology, Department of Clinical Sciences Lund, Lund University, Kioskgatan 5, 22185, Lund, Sweden
- Skåne University Hospital, Department of Rheumatology, Lund, Sweden
| | - Mats Geijer
- Sahlgrenska Academy, Institute of Clinical Sciences, Department of Radiology, University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden
- Section of Radiology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
| | - Lars Erik Kristensen
- Section of Rheumatology, Department of Clinical Sciences Lund, Lund University, Kioskgatan 5, 22185, Lund, Sweden
- Parker Institute, Frederiksberg and Bispebjerg, Department of Rheumatology, Copenhagen University Hospital, Copenhagen, Denmark
| | - Elisabet Lindqvist
- Section of Rheumatology, Department of Clinical Sciences Lund, Lund University, Kioskgatan 5, 22185, Lund, Sweden
- Skåne University Hospital, Department of Rheumatology, Lund, Sweden
| | - Johan K Wallman
- Section of Rheumatology, Department of Clinical Sciences Lund, Lund University, Kioskgatan 5, 22185, Lund, Sweden
- Skåne University Hospital, Department of Rheumatology, Lund, Sweden
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18
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Emad Y, Ragab Y, Hammam N, El-Shaarawy N, Fawzi M, Amer A, El-Makhzangy H, Ismail A, Ibrahim O, Hassan Y, Kamal A, Rasker JJ. The clinical utility of faecal calprotectin in patients with differentiated and undifferentiated spondyloarthritis: Relevance and clinical implications. REUMATOLOGIA CLINICA 2022; 18:69-76. [PMID: 35153039 DOI: 10.1016/j.reumae.2020.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 10/22/2020] [Indexed: 06/14/2023]
Abstract
OBJECTIVES There is cumulative evidence in the literature supporting a potential role of faecal calprotectin (FCP) as a biomarker for gut inflammation in spondyloarthritis (SpA). However its relevance in undifferentiated SpA (USpA) is still uncertain. The aim of the current study is to assess the diagnostic significance of FCP levels in patients with differentiated and undifferentiated SpA. MATERIAL AND METHODS A total of 52 differentiated SpA, 33 USpA and 50 controls could be included. For all patients, clinical evaluation, routine laboratory investigations, FCP levels, and occult blood in stool were performed. When indicated imaging and/or endoscopies were performed. RESULTS The differentiated SpA patients were 12 (23.1%) with ankylosing spondylitis, 21 (40.4%) with psoriatic arthritis, 13 (25%) with ulcerative colitis, 5 (9.6%) with Crohn's disease (CD) and one (1.9%) with reactive arthritis. The mean FCP level in 85 patients correlated with CRP and ESR. Within the SpA group ulcerative colitis and Crohn's disease patients had increased FCP levels compared to other SpA subgroups and USpA patients (p<0.001). The mean FCP levelwas significantly higher in the SpA patients compared to USpA and controls (p<0.001). CONCLUSIONS Elevated FCP levels may identify patients who are most likely to have SpA already in the unclassified phase of the disease. Further studies in different series of patients are needed to evaluate the potential diagnostic and prognostic roles of FCP in both differentiated and undifferentiated phases of the disease.
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Affiliation(s)
- Yasser Emad
- Rheumatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Yasser Ragab
- Radiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Nevin Hammam
- Rheumatology and Rehabilitation Department, Faculty of Medicine, AssiutUniversity, Assiut, Egypt; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Nashwa El-Shaarawy
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Magdy Fawzi
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Arwa Amer
- Rheumatology, Rehabilitation and Physical MedicineDepartment, Faculty of Medicine, Benha University, Benha, Egypt
| | - Hesham El-Makhzangy
- Tropical Medicines Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Ismail
- Dermatology Department, Faculty of Medicine, Al-Azhar University Cairo, Egypt
| | - Ossama Ibrahim
- Morecambe Bay University Hospitals Lancaster, Lancashire, UK
| | - Yosra Hassan
- Clinical pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Kamal
- Orthopedic Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Johannes J Rasker
- Faculty of Behavioural, Management and Social sciences, Department Psychology, Health and Technology, University of Twente, Enschede, The Netherlands
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Rodriguez VR, Sonnenberg E, Proft F, Protopopov M, Schumann M, Kredel LI, Rademacher J, Torgutalp M, Haibel H, Verba M, Siegmund B, Poddubnyy D. Presence of spondyloarthritis associated to higher disease activity and HLA-B27 positivity in patients with early Crohn’s disease: clinical and MRI results from a prospective inception cohort. Joint Bone Spine 2022; 89:105367. [DOI: 10.1016/j.jbspin.2022.105367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 02/07/2022] [Accepted: 02/12/2022] [Indexed: 02/07/2023]
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20
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Feng J, Li J, Li Y, Jin Y, Du F, Chen X. Elevated Serum D-Dimer May Reflect the Presence of Gut Inflammation in Spondyloarthritis. Front Med (Lausanne) 2022; 8:816422. [PMID: 35127771 PMCID: PMC8815704 DOI: 10.3389/fmed.2021.816422] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 12/20/2021] [Indexed: 12/20/2022] Open
Abstract
Background To investigate the association of D-dimer with gut inflammation in spondyloarthritis (SpA). Methods Sixty-five patients with SpA and 70 healthy controls were included. Demographic, clinical, and laboratory parameters were collected. The differences of clinical and laboratory parameters were compared between patients with SpA and healthy controls, and between patients with SpA, with and without gut inflammation. The associations of D-dimer with laboratory data were analyzed. The predictive value of D-dimer was obtained by a receiver operator characteristic (ROC) curve analysis. The independent risk factors for gut inflammation in SpA were investigated by binary logistic regression analysis. Results Patients with SpA had higher D-dimer than healthy controls (P = 0.016). D-dimer was positively correlated with platelet (PLT), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), and negatively correlated with hemoglobin (Hb). Besides, significant differences were observed in D-dimer between SpA patients with and without gut inflammation (P < 0.001). Furthermore, SpA patients with gut inflammation were more likely to have peripheral joint involvement than those without gut inflammation (P < 0.001). The AUC of D-dimer was 0.865 at cut-off value of 0.29 mg/L, with a sensitivity of 82.6%, and a specificity of 81%. Elevated D-dimer (OR = 15.451, 95% CI: 3.030–78.780, P = 0.001) was independently associated with gut inflammation in SpA. Conclusion D-dimer may be a potential biomarker for identifying SpA patients with gut inflammation.
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21
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Wallman JK, Mogard E, Marsal J, Andréasson K, Jöud A, Geijer M, Kristensen LE, Lindqvist E, Olofsson T. Response to: 'Correspondence on: irritable bowel syndrome symptoms in axial spondyloarthritis more common than among healthy controls: is it an overlooked comorbidity?' by Proft et al. Ann Rheum Dis 2022; 81:e10. [PMID: 31892532 DOI: 10.1136/annrheumdis-2019-216752] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 12/16/2019] [Indexed: 11/03/2022]
Affiliation(s)
- Johan Karlsson Wallman
- Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden
- Department of Rheumatology, Skåne University Hospital Lund, Lund, Sweden
| | - Elisabeth Mogard
- Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden
- Department of Rheumatology, Skåne University Hospital Lund, Lund, Sweden
| | - Jan Marsal
- Department of Clinical Sciences Lund, Gastroenterology, Lund University, Lund, Sweden
- Department of Gastroenterology, Skåne University Hospital Lund, Lund, Sweden
| | - Kristofer Andréasson
- Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden
- Department of Rheumatology, Skåne University Hospital Lund, Lund, Sweden
| | - Anna Jöud
- Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden
| | - Mats Geijer
- Department of Radiology, Sahlgrenska University Hospital, Region Västra Götaland and Department of Radiology, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden
- Department of Clinical Sciences Lund, Diagnostic Radiology, Lund University, Lund, Sweden
| | - Lars Erik Kristensen
- Department of Rheumatology, Copenhagen University Hospital, Frederiksberg and Bispebjerg, Parker Institute, Copenhagen, Denmark
| | - Elisabet Lindqvist
- Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden
- Department of Rheumatology, Skåne University Hospital Lund, Lund, Sweden
| | - Tor Olofsson
- Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden
- Department of Rheumatology, Skåne University Hospital Lund, Lund, Sweden
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22
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Proft F, Protopopov M, Rios Rodriguez V, Torgutalp M, Siegmund B, Poddubnyy D. Correspondence on: 'Irritable bowel syndrome symptoms in axial spondyloarthritis more common than among healthy controls: is it an overlooked comorbidity?' by Wallman et al. Ann Rheum Dis 2022; 81:e9. [PMID: 31818807 DOI: 10.1136/annrheumdis-2019-216735] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Accepted: 11/30/2019] [Indexed: 11/04/2022]
Affiliation(s)
- Fabian Proft
- Department of Gastroenterology, Infectiology and Rheumatology, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, Berlin, Germany
| | - Mikhail Protopopov
- Department of Gastroenterology, Infectiology and Rheumatology, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, Berlin, Germany
| | - Valeria Rios Rodriguez
- Department of Gastroenterology, Infectiology and Rheumatology, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, Berlin, Germany
| | - Murat Torgutalp
- Department of Gastroenterology, Infectiology and Rheumatology, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, Berlin, Germany
| | - Britta Siegmund
- Department of Gastroenterology, Infectiology and Rheumatology, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, Berlin, Germany
| | - Denis Poddubnyy
- Department of Gastroenterology, Infectiology and Rheumatology, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, Berlin, Germany
- Epidemiology unit, German Rheumatism Research Centre, Berlin, Germany
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Gubatan J, Holman DR, Puntasecca CJ, Polevoi D, Rubin SJS, Rogalla S. Antimicrobial peptides and the gut microbiome in inflammatory bowel disease. World J Gastroenterol 2021; 27:7402-7422. [PMID: 34887639 PMCID: PMC8613745 DOI: 10.3748/wjg.v27.i43.7402] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/13/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Antimicrobial peptides (AMP) are highly diverse and dynamic molecules that are expressed by specific intestinal epithelial cells, Paneth cells, as well as immune cells in the gastrointestinal (GI) tract. They play critical roles in maintaining tolerance to gut microbiota and protecting against enteric infections. Given that disruptions in tolerance to commensal microbiota and loss of barrier function play major roles in the pathogenesis of inflammatory bowel disease (IBD) and converge on the function of AMP, the significance of AMP as potential biomarkers and novel therapeutic targets in IBD have been increasingly recognized in recent years. In this frontier article, we discuss the function and mechanisms of AMP in the GI tract, examine the interaction of AMP with the gut microbiome, explore the role of AMP in the pathogenesis of IBD, and review translational applications of AMP in patients with IBD.
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Affiliation(s)
- John Gubatan
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Redwood City, CA 94063, United States
| | - Derek R Holman
- Department of Radiology, Molecular Imaging Program at Stanford , Stanford University, Stanford , CA 94305, United States
| | | | - Danielle Polevoi
- Stanford University School of Medicine, Stanford University, Stanford, CA 94063, United States
| | - Samuel JS Rubin
- Stanford University School of Medicine, Stanford University, Stanford, CA 94063, United States
| | - Stephan Rogalla
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Redwood City, CA 94063, United States
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Lubrano E, Luchetti MM, Benfaremo D, Mauro D, Ciccia F, Perrotta FM. Inflammatory bowel disease manifestations in spondyloarthritis: considerations for the clinician. Expert Rev Clin Immunol 2021; 17:1199-1209. [PMID: 34622735 DOI: 10.1080/1744666x.2021.1991315] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Spondyloarthropathies (SpA) are a group of inflammatory arthritis that can involve the spine and/or peripheral joints. Extra-articular manifestations, such as inflammatory bowel disease (IBD), are frequently observed within the clinical manifestations of SpA and are part of the SpA classification criteria. Evidence of IBD is observed in about 6-7% of SpA patients, and a silent, microscopic gut inflammation, could be present in up to 50% of patients. From a pathogenetic point of view, dysregulated microbiome and migration of T lymphocytes and other cells from gut to the joint ('gut-joint' axis) has been recognized, in the context of a common genetic background. AREAS COVERED The aim of this paper is to narratively review the recent evidences on the epidemiology, classification, clinical findings, pathogenesis, diagnosis, and treatment of IBD in patients with SpA and to provide advices for both rheumatologist and gastroenterologist in the management of IBD in SpA. EXPERT OPINION IBD manifestations in SpA frequently increase the burden of the disease and represent a clinical challenge, especially for the diagnosis, assessment, and treatment of patients affected by those conditions. New treatment strategies targeting both articular and intestinal manifestations are now available and may lead to a better outcome.
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Affiliation(s)
- Ennio Lubrano
- Dipartimento Di Medicina E Scienze Della Salute "Vincenzo Tiberio", Università Degli Studi Del Molise, Campobasso, Italy
| | - Michele Maria Luchetti
- Dipartimento Scienze Cliniche E Molecolari, Università Politecnica Delle Marche & Polo Didattico Ospedaliero "Umberto I-g.m. Lancisi-G.Salesi ", Ancona, Italy
| | - Devis Benfaremo
- Dipartimento Scienze Cliniche E Molecolari, Università Politecnica Delle Marche & Polo Didattico Ospedaliero "Umberto I-g.m. Lancisi-G.Salesi ", Ancona, Italy
| | - Daniele Mauro
- Dipartimento Di Medicina Di Precisione, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Francesco Ciccia
- Dipartimento Di Medicina Di Precisione, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Fabio Massimo Perrotta
- Dipartimento Di Medicina E Scienze Della Salute "Vincenzo Tiberio", Università Degli Studi Del Molise, Campobasso, Italy
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Ercalik C, Baskaya MC, Ozdem S, Butun B. Investigation of asymptomatic intestinal inflammation in ankylosing spondylitis by fecal calprotectin. Arab J Gastroenterol 2021; 22:272-277. [PMID: 34531137 DOI: 10.1016/j.ajg.2021.05.020] [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: 02/28/2020] [Revised: 05/10/2021] [Accepted: 05/31/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND AND STUDY AIMS This study aimed to investigate the prevalence of intestinal inflammation in patients with ankylosing spondylitis (AS) by assessing fecal calprotectin (FC) levels and comparing them with those in patients with rheumatoid arthritis (RA) and non-inflammatory rheumatic diseases. Our secondary aim was to correlate FC levels with antirheumatic treatment, nonsteroidal anti-inflammatory drug (NSAID) usage, and disease activity measures. PATIENTS AND METHODS This cross-sectional study included 97 patients with AS fulfilling the modified New York criteria, 48 patients with RA fulfilling the American College of Rheumatology criteria, and 49 patients with non-inflammatory rheumatic diseases. All patients were questioned about intestinal complaints, and symptomatic patients were excluded. Disease activity was measured in the AS and RA patient groups. RESULTS The AS group had a significantly higher FC test positivity rate than the RA group (p = 0.016). Furthermore, the AS group had FC levels that were negatively correlated with disease duration (p = 0.04). FC levels were not correlated with any disease activity index, erythrocyte sedimentation rate, C-reactive protein, uveitis, or peripheral arthritis. Patients with AS who used NSAIDs had significantly higher FC levels than nonusers (p = 0.001). CONCLUSIONS This study revealed that 11% of patients with AS without intestinal complaints had elevated FC levels. FC levels were not correlated with disease activity in AS. Subclinical intestinal inflammation was higher in the early stages of AS. The AS group had a significantly higher FC test positivity than the RA group. In the AS group, NSAID users had significantly higher FC levels than nonusers; thus, no statistically significant difference was observed between biological agent users and nonusers.
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Affiliation(s)
- Cem Ercalik
- Division of Rheumatology, Department of Physical Medicine and Rehabilitation, Akdeniz University, Faculty of Medicine, Antalya, Turkey
| | - Mehmet Cetin Baskaya
- Department of Physical Medicine and Rehabilitation, Akdeniz University, Faculty of Medicine, Antalya, Turkey.
| | - Sebahat Ozdem
- Department of Biochemistry, Akdeniz University, Faculty of Medicine, Antalya, Turkey
| | - Bulent Butun
- Division of Rheumatology, Department of Physical Medicine and Rehabilitation, Akdeniz University, Faculty of Medicine, Antalya, Turkey
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26
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Märker-Hermann E. [Update: enterogenic spondylarthritis]. Z Rheumatol 2021; 80:539-551. [PMID: 34046687 DOI: 10.1007/s00393-021-01014-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2021] [Indexed: 11/30/2022]
Abstract
Spondylarthritis (SpA) is one of the most frequent extraintestinal manifestations of chronic inflammatory bowel disease (IBD). Several arthritogenic enterobacterial infections can induce sequelae such as reactive SpA. Studies on the gut-synovium axis in view of genetic, immunological, clinical and therapeutic aspects has made enterogenic SpA a model disease of all forms of SpA. The same applies for investigating IBD, as subclinical gut inflammation seen in SpA patients has provided significant evidence for a better understanding of mucosa-associated early immune events in Crohn's disease (CD). This article summarizes the pathognomonic clinical features, diagnostic steps, differential diagnosis and current pathogenetic models of enterogenic SpA. Knowledge of pathogenetic contexts leads to concrete treatment recommendations. These vary individually depending on the underlying IBD, on the inflammatory intestinal or rheumatic activity and on the rheumatological manifestation pattern.
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Affiliation(s)
- Elisabeth Märker-Hermann
- Klinik Innere Medizin IV Rheumatologie, klinische Immunologie und Nephrologie, Helios Dr. Horst Schmidt-Kliniken Wiesbaden, Ludwig-Erhard-Str. 100, 65199, Wiesbaden, Deutschland.
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27
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Cardoneanu A, Cozma S, Rezus C, Petrariu F, Burlui AM, Rezus E. Characteristics of the intestinal microbiome in ankylosing spondylitis. Exp Ther Med 2021; 22:676. [PMID: 33986841 PMCID: PMC8112129 DOI: 10.3892/etm.2021.10108] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 03/26/2021] [Indexed: 12/16/2022] Open
Abstract
The importance of intestinal microbiota in the development of various systemic diseases has been highlighted over time. Ankylosing spondylitis (AS) is a systemic disease with a complex pathogenesis involving a particular genetic marker and distinctive environmental triggers such as a specific gut dysbiosis. We conducted a prospective case-control study which included 60 subjects from Iasi Rehabilitation Hospital: 28 AS cases and 32 healthy controls. Intestinal microbiota analysis was performed by real-time polymerase chain reaction (qPCR) in stool samples. We performed the quantitative analysis of gut microbiome, focusing both on anti-inflammatory (Bifidobacterium, Lactobacillus, Faecalibacterium prausnitzii) and pro-inflammatory (Bacteroides, Escherichia coli) species. Overall, intestinal bacterial diversity in the AS group was decreased compared to that noted in the control. A significantly decreased level of Clostridium leptum was observed, associated with an increased level of Escherichia coli. We showed correlations between laboratory tests (liver and kidney functional tests, inflammatory syndrome), the presence of HLA-B27, smoker status, the forms of AS with peripheral arthritis vs. pure axial forms and bacterial structures. No significant correlations were shown for disease activity scores, radiological stage of sacroiliitis or for body mass index. Our findings support that the intestinal microbiome in AS patients has a special signature characterized by an inflammatory status. Numerous environmental, genetical, clinical and paraclinical factors can lead to changes in gut bacterial diversity in these cases.
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Affiliation(s)
- Anca Cardoneanu
- Department of Rheumatology and Physiotherapy, Grigore T Popa University of Medicine and Pharmacy, Faculty of Medicine, 700115 Iasi, Romania
| | - Sebastian Cozma
- Department of Surgery (II), Grigore T Popa University of Medicine and Pharmacy, Faculty of Medicine, 700115 Iasi, Romania
| | - Ciprian Rezus
- Department of Internal Medicine, Grigore T Popa University of Medicine and Pharmacy, Faculty of Medicine, 700115 Iasi, Romania
| | - Florin Petrariu
- Department of Preventive Medicine and Interdisciplinarity, Grigore T Popa University of Medicine and Pharmacy, Faculty of Medicine, 700115 Iasi, Romania
| | - Alexandra Maria Burlui
- Department of Rheumatology and Physiotherapy, Grigore T Popa University of Medicine and Pharmacy, Faculty of Medicine, 700115 Iasi, Romania
| | - Elena Rezus
- Department of Rheumatology and Physiotherapy, Grigore T Popa University of Medicine and Pharmacy, Faculty of Medicine, 700115 Iasi, Romania
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28
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Qaiyum Z, Lim M, Inman RD. The gut-joint axis in spondyloarthritis: immunological, microbial, and clinical insights. Semin Immunopathol 2021; 43:173-192. [PMID: 33625549 DOI: 10.1007/s00281-021-00845-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 01/27/2021] [Indexed: 12/13/2022]
Abstract
The strong genetic and clinical overlaps between spondyloarthritis (SpA) and inflammatory bowel disease (IBD) have placed much needed focus on the gut-joint axis of inflammation in SpA, leading to three key hypotheses that attempt to unravel this complex relationship. The arthritogenic peptide hypothesis and the aberrant cellular trafficking hypothesis have been put forth to rationalize the manner by which the innate and adaptive immune systems cooperate and converge during SpA pathogenesis. The bacterial dysbiosis hypothesis discusses how changes in the microbiome lead to architectural and immunological consequences in SpA. These theories are not mutually exclusive, but can provide an explanation as to why subclinical gut inflammation may sometimes precede joint inflammation in SpA patients, thereby implying a causal relationship. Such investigations will be important in informing therapeutic decisions which may be common to both SpA and IBD. However, these hypotheses can also offer insights for a coincident inflammatory relationship between the gut and the joint, particularly when assessing the immunological players involved. Insights from understanding how these systems might affect the gut and joint differently will be equally imperative to address where the therapeutic differences lie between the two diseases. Collectively, this knowledge has practical implications in predicting the likelihood of IBD development in SpA or presence of coincident SpA-IBD, uncovering novel therapeutic targets, and redesigning currently approved treatments. It is evident that a multidisciplinary approach between the rheumatology and gastroenterology fields cannot be ignored, when it comes to the care of SpA patients at risk of IBD or vice versa.
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Affiliation(s)
- Zoya Qaiyum
- Schroeder Arthritis Institute, University Health Network, 60 Leonard Avenue, 5, Toronto, Ontario, KD-408, Canada
| | - Melissa Lim
- Schroeder Arthritis Institute, University Health Network, 60 Leonard Avenue, 5, Toronto, Ontario, KD-408, Canada
| | - Robert D Inman
- Schroeder Arthritis Institute, University Health Network, 60 Leonard Avenue, 5, Toronto, Ontario, KD-408, Canada.
- Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
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29
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CisarÒ F, Pizzol A, Rigazio C, Calvo PL. Fecal calprotectin in the pediatric population: a 2020 update. Minerva Pediatr 2020; 72:514-522. [PMID: 32731735 DOI: 10.23736/s0026-4946.20.06002-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Calprotectin is a calcium and zinc-binding protein, formed by a hetero complex of S100A8 and S100A9 proteins, which belong to the S-100 protein family consisting in more than 20 different proteins with a tissue-specific expression pattern. This protein is secreted extracellularly from stimulated neutrophils or released by cell disruption or death. The presence of calprotectin in feces quantitatively relates to neutrophil migration toward the gastrointestinal (GI) tract; thus, it represents a useful marker of intestinal inflammation. Fecal calprotectin (FC) has been proven largely useful for determining the inflammatory origin of GI symptoms differentiating between organic and non-organic diseases. Indeed, increased FC levels are also seen in gastroenteritis, microscopic colitis, polyps, malignancies and cystic fibrosis. To date, there are many evidences regarding usefulness in the detection of fecal calprotectin for the management of gastrointestinal disorders, both in children and adults but, especially in the pediatric population, still clear indications for its use are lacking. Its incorporation in primary care reduces the risk of missing an organic disease and facilitates the indication for expensive and invasive investigations as colonoscopy. We herein review and discuss the last evidence on the usefulness of FC in children, with its current indications and future prospective.
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Affiliation(s)
- Fabio CisarÒ
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza, Turin, Italy -
| | - Antonio Pizzol
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza, Turin, Italy
| | - Caterina Rigazio
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza, Turin, Italy
| | - Pier L Calvo
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza, Turin, Italy
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30
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Emad Y, Ragab Y, Hammam N, El-Shaarawy N, Fawzi M, Amer A, El-Makhzangy H, Ismail A, Ibrahim O, Hassan Y, Kamal A, Rasker JJ. The Clinical Utility of Faecal Calprotectin in Patients with Differentiated and Undifferentiated Spondyloarthritis: Relevance and Clinical Implications. REUMATOLOGIA CLINICA 2020; 18:S1699-258X(20)30238-2. [PMID: 33234498 DOI: 10.1016/j.reuma.2020.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 10/17/2020] [Accepted: 10/22/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVES There is cumulative evidence in the literature supporting a potential role of faecal calprotectin (FCP) as a biomarker for gut inflammation in spondyloarthritis (SpA). However its relevance in undifferentiated SpA (USpA) is still uncertain. The aim of the current study is to assess the diagnostic significance of FCP levels in patients with differentiated and undifferentiated SpA. MATERIAL AND METHODS A total of 52 differentiated SpA, 33 USpA and 50 controls could be included. For all patients, clinical evaluation, routine laboratory investigations, FCP levels, and occult blood in stool were performed. When indicated imaging and/or endoscopies were performed. RESULTS The differentiated SpA patients were 12 (23.1%) with ankylosing spondylitis, 21 (40.4%) with psoriatic arthritis, 13 (25%) with ulcerative colitis, 5 (9.6%) with Crohn's disease (CD) and one (1.9%) with reactive arthritis. The mean FCP level in 85 patients correlated with CRP and ESR. Within the SpA group ulcerative colitis and Crohn's disease patients had increased FCP levels compared to other SpA subgroups and USpA patients (p<0.001). The mean FCP levelwas significantly higher in the SpA patients compared to USpA and controls (p<0.001). CONCLUSIONS Elevated FCP levels may identify patients who are most likely to have SpA already in the unclassified phase of the disease. Further studies in different series of patients are needed to evaluate the potential diagnostic and prognostic roles of FCP in both differentiated and undifferentiated phases of the disease.
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Affiliation(s)
- Yasser Emad
- Rheumatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Yasser Ragab
- Radiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Nevin Hammam
- Rheumatology and Rehabilitation Department, Faculty of Medicine, AssiutUniversity, Assiut, Egypt; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Nashwa El-Shaarawy
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Magdy Fawzi
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Arwa Amer
- Rheumatology, Rehabilitation and Physical MedicineDepartment, Faculty of Medicine, Benha University, Benha, Egypt
| | - Hesham El-Makhzangy
- Tropical Medicines Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Ismail
- Dermatology Department, Faculty of Medicine, Al-Azhar University Cairo, Egypt
| | - Ossama Ibrahim
- Morecambe Bay University Hospitals Lancaster, Lancashire, UK
| | - Yosra Hassan
- Clinical pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Kamal
- Orthopedic Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Johannes J Rasker
- Faculty of Behavioural, Management and Social sciences, Department Psychology, Health and Technology, University of Twente, Enschede, The Netherlands
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31
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Couderc M, Pereira B, Schaeverbeke T, Thomas T, Chapurlat R, Gaudin P, Morel J, Dougados M, Soubrier M. GlutenSpA trial: protocol for a randomised double-blind placebo-controlled trial of the impact of a gluten-free diet on quality of life in patients with axial spondyloarthritis. BMJ Open 2020; 10:e038715. [PMID: 33444189 PMCID: PMC7682451 DOI: 10.1136/bmjopen-2020-038715] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Subclinical intestinal inflammation and gut dysbiosis have been reported in patients with spondyloarthritis (SpA). In common practice, rheumatologists are increasingly confronted with patients with inflammatory rheumatism who are on gluten-free diets (GFDs), despite the lack of reliable data from controlled studies. This study aims to determine the impact of a GFD on the quality of life of patients with axial SpA. METHODS AND ANALYSIS The GlutenSpA study is a 24-week, randomised, double-blinded, placebo-controlled, multicentre trial. Patients with axial SpA (n=200) will follow a 16-week GFD and be randomly assigned (1:1) to an experimental or control arm. In the experimental arm with receive at least 6 gluten-free breads per day + 200 g of gluten-free penne pasta per week + 6 rice flavour capsules per day. The control arm will receive at least 6 gluten-containing breads per day + 200 g of gluten-containing penne pasta per week + 6 vital gluten-containing capsules per day. The primary end-point is the variation in Assessment of SpondyloArthritis International Society-Health Index (ASAS-HI) questionnaire between week 16 and baseline. A second open-label period of 8 weeks will follow the intervention period, during which the patient will be free to decide whether they will follow the GFD. The secondary outcomes comprise several patient-reported outcomes (SpA activity (Bath Ankylosing Spondylitis Disease Activity Index)), fatigue (Functional Assessment of Chronic Illness Therapy), depression (Hospital Anxiety and Depression Scale), functional disability index (Bath Ankylosing Spondylitis Functional Index)), variations in body mass index and Homeostasis Model Assessment Index and variations in the abundance and type of bacterial species found in the gut microbiota for a subgroup of patients (n=40). The data will be analysed using the intention-to-treat principle.The regional ethics committee (CPP Nord-ouest IV) has approved the study (IDRCB 2018-A00309-46). The results of the trial will be submitted for publication in peer-reviewed journals. The authors have no relationship that may have influenced the submitted work. TRIAL REGISTRATION NUMBER NCT04274374.
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Affiliation(s)
- Marion Couderc
- Rheumatology, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Bruno Pereira
- Biostatistical Unit, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | | | | | | | - Philippe Gaudin
- Rheumatology, CHU Grenoble Alpes, Grenoble, Rhône-Alpes, France
| | - Jacques Morel
- Rheumatology, CHU Montpellier, Montpellier, Languedoc-Roussillon, France
| | - Maxime Dougados
- Rheumatology, Cochin Institute, Paris, Île-de-France, France
| | - Martin Soubrier
- Rheumatology, CHU Clermont-Ferrand, Clermont-Ferrand, France
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32
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Paley EL. Discovery of Gut Bacteria Specific to Alzheimer's Associated Diseases is a Clue to Understanding Disease Etiology: Meta-Analysis of Population-Based Data on Human Gut Metagenomics and Metabolomics. J Alzheimers Dis 2020; 72:319-355. [PMID: 31561379 DOI: 10.3233/jad-190873] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Alzheimer's disease (AD)-associated sequence (ADAS) of cultured fecal bacteria was discovered in human gut targeted screening. This study provides important information to expand our current understanding of the structure/activity relationship of ADAS and putative inhibitors/activators that are potentially involved in ADAS appearance/disappearance. The NCBI database analysis revealed that ADAS presents at a large proportion in American Indian Oklahoman (C&A) with a high prevalence of obesity/diabetes and in colorectal cancer (CRC) patients from the US and China. An Oklahoman non-native group (NNI) showed no ADAS. Comparison of two large US populations reveals that ADAS is more frequent in individuals aged ≥66 and in females. Prevalence and levels of fecal metabolites are altered in the C&A and CRC groups versus controls. Biogenic amines (histamine, tryptamine, tyramine, phenylethylamine, cadaverine, putrescine, agmatine, spermidine) that present in food and are produced by gut microbiota are significantly higher in C&A (e.g., histamine/histidine 95-fold) versus NNI (histamine/histidine 16-fold). The majority of these bio-amines are cytotoxic at concentrations found in food. Inositol phosphate signaling implicated in AD is altered in C&A and CRC. Tryptamine stimulated accumulation of inositol phosphate. The seizure-eliciting tryptamine induced cytoplasmic vacuolization and vesiculation with cell fragmentation. Present additions of ADAS-carriers at different ages including infants led to an ADAS-comprising human sample size of 2,830 from 27 studies from four continents (North America, Australia, Asia, Europe). Levels of food-derived monoamine oxidase inhibitors and anti-bacterial compounds, the potential modulators of ADAS-bacteria growth and biogenic amine production, were altered in C&A versus NNI. ADAS is attributable to potentially modifiable risk factors of AD associated diseases.
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Affiliation(s)
- Elena L Paley
- Expert Biomed, Inc., Miami, FL, USA.,Stop Alzheimers Corp, Miami, FL, USA
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33
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Ma Y, Fan D, Xu S, Deng J, Gao X, Guan S, Pan F. Calprotectin in spondyloarthritis: A systematic review and meta-analysis. Int Immunopharmacol 2020; 88:106948. [PMID: 32892074 DOI: 10.1016/j.intimp.2020.106948] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 08/11/2020] [Accepted: 08/27/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVE There is still an unmet need for a simple and reliable biomarker for diagnosis and disease activity of spondyloarthritis. Recent studies indicated that calprotectin could act as a biomarker for spondyloarthritis. Therefore, this systematic review and meta-analysis aims to evaluate the levels of serum and fecal calprotectin in spondyloarthritis and the associations with disease activity. METHODS PubMed, Web of Science and Cochrane Library were comprehensively searched from inception to July 1st, 2019. The pooled standard mean differences (SMDs) were used to estimate the differences of the levels of serum and fecal calprotectin between spondyloarthritis patients and controls. Spearman correlation coefficients were used for evaluating the associations between the levels of serum and fecal calprotectin and disease activity of spondyloarthritis patients. The use of fixed-effect or random-effects model depended on heterogeneity. RESULTS Among 257 searched studies, 20 studies were finally included for analysis. Serum and fecal calprotectin were both significantly increased in spondyloarthritis patients compared to matched controls (SMD = 1.49, 95% CI = 0.91 to 2.08; SMD = 2.29, 95% CI = 0.25 to 4.33). The pooled correlation coefficients between serum or fecal calprotectin and CRP, ESR, BASDAI and BASFI were 0.353, 0.228, 0.225, 0.131 and 0.185, 0.163, 0.280, 0.196 respectively. CONCLUSION Our study indicated that serum and fecal calprotectin were significantly increased in spondyloarthritis patients, and associated with disease activity. Serum and fecal calprotectin were potential biomarkers for the diagnosis and disease activity of spondyloarthritis.
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Affiliation(s)
- Yubo Ma
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China
| | - Dazhi Fan
- Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan, Guangdong, China
| | - Shanshan Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China
| | - Jixiang Deng
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China
| | - Xing Gao
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China
| | - Shiyang Guan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China
| | - Faming Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China.
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Magro F, Estevinho MM. Is Faecal Calprotectin Important in Detecting Silent Gut Inflammation in Seronegative Arthropathies? J Crohns Colitis 2020; 14:886-887. [PMID: 32016384 DOI: 10.1093/ecco-jcc/jjaa011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Fernando Magro
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.,Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal.,MedInUP, Center for Drug Discovery and Innovative Medicines, Porto, Portugal
| | - Maria Manuela Estevinho
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.,Department of Gastroenterology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal
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35
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Kang KY, Park SH, Hong YS. Relationship between faecal calprotectin and inflammation in peripheral joints and entheses in axial spondyloarthritis. Scand J Rheumatol 2020; 49:397-404. [PMID: 32657633 DOI: 10.1080/03009742.2020.1748707] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Objectives: To compare faecal calprotectin levels according to the type of manifestation and to investigate factors associated with increases in faecal calprotectin in patients with axial spondyloarthritis (axSpA). Method: The study enrolled 190 patients fulfilling the imaging arm of the Assessment of SpondyloArthritis international Society axSpA criteria. Faecal calprotectin levels were measured in an enzyme-linked immunosorbent assay. Systemic inflammatory markers and the Ankylosing Spondylitis Disease Activity Score (ASDAS) were also assessed. Peripheral joint involvement was assessed using the 44-joint examination and Spondyloarthritis Research Consortium of Canada Enthesitis Index. Results: Of 190 patients, 34 (18%) had increased faecal calprotectin levels. These patients were more likely to have ongoing peripheral arthritis and enthesitis (p = 0.016 and 0.001, respectively). A history of psoriasis and uveitis, or current uveitis symptoms, had no bearing on faecal calprotectin levels. Faecal calprotectin levels increased along with ASDAS-C-reactive protein (CRP), and correlated with ASDAS-erythrocyte sedimentation rate (ESR) (r = 0.240, p = 0.001), ASDAS-CRP (r = 0.162, p = 0.025), ESR (r = 0.228, p = 0.002), and CRP levels (0.258, p < 0.001). Tender joint and swollen joint counts also correlated with faecal calprotectin levels (r = 0.252 and 0.205, p < 0.001 and p = 0.005, respectively). Faecal calprotectin levels were higher in patients with current peripheral symptoms (p = 0.003). Peripheral symptoms were independently associated with increased faecal calprotectin levels (odds ratio = 4.083; 95% confidence interval 1.580-10.556). Conclusions: Faecal calprotectin levels in axSpA patients were associated with disease activity. Subclinical gut inflammation (assessed by measuring faecal calprotectin) in axSpA is more closely related to peripheral joint inflammation than to axial joint inflammation.
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Affiliation(s)
- K Y Kang
- Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.,Division of Rheumatology, Department of Internal Medicine, Incheon Saint Mary's Hospital, College of Medicine, The Catholic University of Korea , Incheon, Republic of Korea
| | - S-H Park
- Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea
| | - Y S Hong
- Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.,Division of Rheumatology, Department of Internal Medicine, Incheon Saint Mary's Hospital, College of Medicine, The Catholic University of Korea , Incheon, Republic of Korea
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36
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Di Jiang C, Raine T. IBD considerations in spondyloarthritis. Ther Adv Musculoskelet Dis 2020; 12:1759720X20939410. [PMID: 32695235 PMCID: PMC7350041 DOI: 10.1177/1759720x20939410] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 06/12/2020] [Indexed: 12/18/2022] Open
Abstract
Spondyloarthritis (SpA) may be regarded a family of auto-inflammatory conditions with inflammation focused on the joints. These form part of a wider family of immune-mediated inflammatory diseases, which include inflammatory bowel diseases (IBD). These conditions share common elements of pathophysiology and it is perhaps unsurprising, therefore, that individuals with SpA frequently manifest gastrointestinal inflammation, to which the physician managing the patient with SpA must be alert. In this article, we review the shared epidemiology and pathophysiology of these conditions, before discussing approaches to diagnosis and management of inflammatory gastrointestinal pathology in patients seen in rheumatology clinics. In particular, we discuss the difference between non-specific gastrointestinal inflammation commonly described in this patient group and the more specific diagnosis of Crohn's disease or ulcerative colitis. We describe the appropriate diagnostic workup for patients suspected of having IBD. In addition, we discuss how a diagnosis of IBD can inform treatment selection, highlighting important differences in treatment choice, drug dosing, monitoring and drug safety for this particular comorbid patient population.
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Affiliation(s)
- Caroline Di Jiang
- Department of Gastroenterology, Addenbrooke’s Hospital, Cambridge, UK
| | - Tim Raine
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
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37
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Bieber A, Masala IF, Mader R, Atzeni F. Differences between diffuse idiopathic skeletal hyperostosis and spondyloarthritis. Immunotherapy 2020; 12:749-756. [DOI: 10.2217/imt-2020-0045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Diffuse idiopathic skeletal hyperostosis (DISH) is a skeletal syndrome that has been known for more than 70 years. Yet, its pathogenesis and treatment options are still under investigation. DISH and spondyloarthritidies may manifest itself clinically as very similar disorders causing impaired axial flexibility, axial pain and peripheral tendinopathies. On the other hand, these two processes are different in many ways, from different genetic and metabolic predispositions, to different clinical and imaging manifestations, and at last, a different attitude toward treatment. The knowledge of the similarities and differences between DISH and spondyloarthritidies can guide the clinician toward a better diagnostic and treatment approach. This review tries to emphasize these details.
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Affiliation(s)
- Amir Bieber
- Rheumatic diseases Unit, Ha'Emek MC, Afula, Israel
| | | | - Reuven Mader
- Rheumatic diseases Unit, Ha'Emek MC, Afula, Israel
| | - Fabiola Atzeni
- Trauma & Orthopedic Unit, Santissima Trinità Hospital, Cagliari, Italy
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, Italy
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38
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Abstract
The term axial spondyloarthritis (axSpA) encompasses a heterogeneous group of diseases that have variable presentations, extra-articular manifestations and clinical outcomes, and that will respond differently to treatments. The prototypical type of axSpA, ankylosing spondylitis, is thought to be caused by interaction between the genetically primed host immune system and gut microbiota. Currently used biomarkers such as HLA-B27 status, C-reactive protein and erythrocyte sedimentation rate have, at best, moderate diagnostic and predictive value. Improved biomarkers are needed for axSpA to assist with early diagnosis and to better predict treatment responses and long-term outcomes. Advances in a range of 'omics' technologies and statistical approaches, including genomics approaches (such as polygenic risk scores), microbiome profiling and, potentially, transcriptomic, proteomic and metabolomic profiling, are making it possible for more informative biomarker sets to be developed for use in such clinical applications. Future developments in this field will probably involve combinations of biomarkers that require novel statistical approaches to analyse and to produce easy to interpret metrics for clinical application. Large publicly available datasets from well-characterized case-cohort studies that use extensive biological sampling, particularly focusing on early disease and responses to medications, are required to establish successful biomarker discovery and validation programmes.
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39
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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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40
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Burisch J, Eigner W, Schreiber S, Aletaha D, Weninger W, Trauner M, Reinisch W, Narula N. Risk for development of inflammatory bowel disease under inhibition of interleukin 17: A systematic review and meta-analysis. PLoS One 2020; 15:e0233781. [PMID: 32459816 PMCID: PMC7252630 DOI: 10.1371/journal.pone.0233781] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 05/12/2020] [Indexed: 12/20/2022] Open
Abstract
Objective Cases of inflammatory bowel disease (IBD) during treatment with interleukin (IL)-17 antagonists have been reported from trials in psoriasis, psoriatic arthritis, and ankylosing spondylitis. The aim of this study was to assess the overall risk for development of IBD due to IL-17 inhibition. Design Systematic review and meta-analysis of studies conducted 2010–2018 of treatment with IL-17 antagonists in patients with psoriasis, psoriatic arthritis, ankylosing spondylitis, and rheumatoid arthritis. We compared risk of IBD development in anti-IL-17 treated patients compared to placebo treatments. We also computed incident rates of IBD overall. A ‘worst case scenario’ defining subjects ambiguous for prevalent versus incident cases for the latter was also applied. Results Sixty-six studies of 14,390 patients exposed to induction and 19,380 patients exposed to induction and/or maintenance treatment were included. During induction, 11 incident cases of IBD were reported, whereas 33 cases were diagnosed during the entire treatment period. There was no difference in the pooled risk of new-onset IBD during induction studies for both the best-case [risk difference (RD) 0.0001 (95% CI: -0.0011, 0.0013)] and worst-case scenario [RD 0.0008 (95% CI: -0.0005, 0.0022)]. The risk of IBD was not different from placebo when including data from maintenance and long-term extension studies [RD 0.0007 (95% CI: -0.0023, 0.0036) and RD 0.0022 (95% CI: -0.0010, 0.0055), respectively]. Conclusions The risk for development of IBD in patients treated with IL-17 antagonists is not elevated. Prospective surveillance of patients treated with IL-17 antagonists with symptom and biomarker assessments is warranted to assess for onset of IBD in these patients.
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MESH Headings
- Antibodies, Monoclonal/adverse effects
- Antibodies, Monoclonal/therapeutic use
- Arthritis, Psoriatic/drug therapy
- Arthritis, Psoriatic/epidemiology
- Arthritis, Psoriatic/immunology
- Arthritis, Psoriatic/pathology
- Arthritis, Rheumatoid/drug therapy
- Arthritis, Rheumatoid/epidemiology
- Arthritis, Rheumatoid/immunology
- Arthritis, Rheumatoid/pathology
- Female
- Humans
- Inflammatory Bowel Diseases/chemically induced
- Inflammatory Bowel Diseases/epidemiology
- Inflammatory Bowel Diseases/immunology
- Interleukin-17/antagonists & inhibitors
- Interleukin-17/immunology
- Male
- Randomized Controlled Trials as Topic
- Spondylitis, Ankylosing/drug therapy
- Spondylitis, Ankylosing/epidemiology
- Spondylitis, Ankylosing/immunology
- Spondylitis, Ankylosing/pathology
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Affiliation(s)
- Johan Burisch
- Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Wolfgang Eigner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Stefan Schreiber
- Department of Gastroenterology, Christian-Albrechts-Universität zu Kiel, Kiel, Deutschland
| | - Daniel Aletaha
- Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Weninger
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Walter Reinisch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- * E-mail:
| | - Neeraj Narula
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
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41
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Kyle BD, Agbor TA, Sharif S, Chauhan U, Marshall J, Halder SLS, Ip S, Khan WI. Fecal Calprotectin, CRP and Leucocytes in IBD Patients: Comparison of Biomarkers With Biopsy Results. J Can Assoc Gastroenterol 2020; 4:84-90. [PMID: 33855266 PMCID: PMC8023817 DOI: 10.1093/jcag/gwaa009] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background This study aimed to compare fecal calprotectin (FC) levels with other commonly used parameters as part of patient care during evaluation for inflammatory bowel disease (IBD). Methods We recruited adult IBD patients with ulcerative colitis (UC) and Crohn's disease (CD) and compared the results of the patient's biopsy results (i.e., inflamed versus noninflamed) for six sites (i.e., ileum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum) with concentrations of C-reactive protein (CRP), total leucocytes and fecal calprotectin (FC). Results We found that FC was significantly elevated in a concentration-dependent manner that correlated with the number of active inflammation sites reported in biopsy. Although CRP and leucocyte measurements trended upwards in line with inflammation reported from biopsy, the results were highly variable and highlighted poor reliability of these biomarkers for indicating IBD inflammation. Conclusions These results strongly suggest that FC correlates best with biopsy reports and is a superior marker than CRP and leucocytes.
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Affiliation(s)
- Barry D Kyle
- DynaLIFE Medical Labs, Edmonton, Alberta, Canada.,Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.,Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Terence A Agbor
- DynaLIFE Medical Labs, Edmonton, Alberta, Canada.,Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.,Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Shajib Sharif
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.,Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Usha Chauhan
- Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.,Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - John Marshall
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.,Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.,Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Smita L S Halder
- Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.,Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Stephen Ip
- Grey Nuns Hospital, Edmonton, Alberta, Canada
| | - Waliul I Khan
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.,Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.,Hamilton Health Sciences, Hamilton, Ontario, Canada
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Kiltz U, Braun J, Becker A, Chenot JF, Dreimann M, Hammel L, Heiligenhaus A, Hermann KG, Klett R, Krause D, Kreitner KF, Lange U, Lauterbach A, Mau W, Mössner R, Oberschelp U, Philipp S, Pleyer U, Rudwaleit M, Schneider E, Schulte TL, Sieper J, Stallmach A, Swoboda B, Winking M. [Long version on the S3 guidelines for axial spondyloarthritis including Bechterew's disease and early forms, Update 2019 : Evidence-based guidelines of the German Society for Rheumatology (DGRh) and participating medical scientific specialist societies and other organizations]. Z Rheumatol 2020; 78:3-64. [PMID: 31784900 DOI: 10.1007/s00393-019-0670-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- U Kiltz
- Rheumazentrum Ruhrgebiet, Ruhr-Universität Bochum, Claudiusstr. 45, 44649, Herne, Deutschland.
| | - J Braun
- Rheumazentrum Ruhrgebiet, Ruhr-Universität Bochum, Claudiusstr. 45, 44649, Herne, Deutschland
| | | | - A Becker
- Allgemeinmedizin, präventive und rehabilitative Medizin, Universität Marburg, Karl-von-Frisch-Str. 4, 35032, Marburg, Deutschland
| | | | - J-F Chenot
- Universitätsmedizin Greifswald, Fleischmann Str. 6, 17485, Greifswald, Deutschland
| | - M Dreimann
- Zentrum für Operative Medizin, Klinik und Poliklinik für Unfall‑, Hand- und Wiederherstellungschirurgie, Universitätsklinikum Hamburg-Eppendorf (UKE), Martinistraße 52, 20251, Hamburg, Deutschland
| | | | - L Hammel
- Geschäftsstelle des Bundesverbandes der DVMB, Metzgergasse 16, 97421, Schweinfurt, Deutschland
| | | | - A Heiligenhaus
- Augenzentrum und Uveitis-Zentrum, St. Franziskus Hospital, Hohenzollernring 74, 48145, Münster, Deutschland
| | | | - K-G Hermann
- Institut für Radiologie, Charité Berlin, Charitéplatz 1, 10117, Berlin, Deutschland
| | | | - R Klett
- Praxis Manuelle & Osteopathische Medizin, Fichtenweg 17, 35428, Langgöns, Deutschland
| | | | - D Krause
- , Friedrich-Ebert-Str. 2, 45964, Gladbeck, Deutschland
| | - K-F Kreitner
- Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsmedizin Mainz, Langenbeckstr. 1, 55131, Mainz, Deutschland
| | - U Lange
- Kerckhoff-Klinik, Rheumazentrum, Osteologie & Physikalische Medizin, Benekestr. 2-8, 61231, Bad Nauheim, Deutschland
| | | | - A Lauterbach
- Schule für Physiotherapie, Orthopädische Universitätsklinik Friedrichsheim, Marienburgstraße 2, 60528, Frankfurt, Deutschland
| | | | - W Mau
- Institut für Rehabilitationsmedizin, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, 06097, Halle (Saale), Deutschland
| | - R Mössner
- Klinik für Dermatologie, Universitätsmedizin Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Deutschland
| | | | - U Oberschelp
- , Barlachstr. 6, 59368, Werne a.d. L., Deutschland
| | | | - S Philipp
- Praxis für Dermatologie, Bernauer Str. 66, 16515, Oranienburg, Deutschland
| | - U Pleyer
- Campus Virchow-Klinikum, Charité Centrum 16, Klinik f. Augenheilkunde, Charité, Augustenburger Platz 1, 13353, Berlin, Deutschland
| | - M Rudwaleit
- Klinikum Bielefeld, An der Rosenhöhe 27, 33647, Bielefeld, Deutschland
| | - E Schneider
- Abt. Fachübergreifende Frührehabilitation und Sportmedizin, St. Antonius Hospital, Dechant-Deckersstr. 8, 52249, Eschweiler, Deutschland
| | - T L Schulte
- Klinik für Orthopädie und Unfallchirurgie, Orthopädische Universitätsklinik, Ruhr-Universität Bochum, Gudrunstr. 65, 44791, Bochum, Deutschland
| | - J Sieper
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV, Universitätsklinikum Jena, Am Klinikum 1, 07743, Jena, Deutschland
| | | | - B Swoboda
- Abteilung für Orthopädie und Rheumatologie, Orthopädische Universitätsklinik, Malteser Waldkrankenhaus St. Marien, 91054, Erlangen, Deutschland
| | | | - M Winking
- Zentrum für Wirbelsäulenchirurgie, Klinikum Osnabrück, Am Finkenhügel 3, 49076, Osnabrück, Deutschland
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Rauber C, Awad M, Koschny R, Sauer P, Mehrabi A, Gath P, Weiss KH, Gotthardt DN, Rupp C. Biliary calprotectin, lactoferrin and dimeric pyruvate kinase after liver transplantation are associated with biliary damage and graft survival in a case-control study. Clin Res Hepatol Gastroenterol 2020; 44:38-48. [PMID: 31201006 DOI: 10.1016/j.clinre.2019.05.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 05/05/2019] [Accepted: 05/09/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND After liver transplantation (LT), biliary complications are associated with reduced graft survival. We tested inflammation markers for their association with biliary damage and graft loss in bile. MATERIAL AND METHODS The study design was a retrospective case-control study. Calprotectin, lactoferrin and pyruvate kinase were measured in endoscopically retrieved bile with ELISA. RESULTS Calprotectin and lactoferrin were significantly higher in bile of ischemic-type biliary lesions and donor duct non-anastomotic strictures than in control, bile leakage, Cytomegalovirus infection, anastomotic stricture or acute cellular rejection patients (p<0.001) independent of serum liver values at endoscopy. Calprotectin (p=0.02) was independently associated with retransplantation free survival in multivariate analysis, as was γGT (p=0.03) but not ERC radiographic classification of the bile duct or cold ischemia time. CONCLUSION Calprotectin and lactoferrin are bile markers for biliary damage and are associated with re-transplantation free survival. They can differentiate progressive biliary damage from non-biliary liver value alterations after LT.
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Affiliation(s)
- Conrad Rauber
- Department of Gastroenterology, University Hospital Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany; Université Paris-Sud, Université Paris-Saclay, 91400 Paris, France; Gustave Roussy Cancer Campus (GRCC), 94800 Villejuif, France.
| | - Miriam Awad
- Department of Gastroenterology, University Hospital Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany
| | - Ronald Koschny
- Department of Gastroenterology, University Hospital Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany
| | - Peter Sauer
- Department of Gastroenterology, University Hospital Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany
| | - Philip Gath
- Department of Gastroenterology and Hepatology, Hospital Ludwigshafen, 67063 Ludwigshafen, Germany
| | - Karl-Heinz Weiss
- Department of Gastroenterology, University Hospital Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany
| | - Daniel Nils Gotthardt
- Department of Gastroenterology, University Hospital Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany
| | - Christian Rupp
- Department of Gastroenterology, University Hospital Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany
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Li R, Zhao X, Dong J, Zhu D, Wang T, Yang S, Zhao Z, Xiao N. Evaluation of a fluorescent immunochromatography test for fecal calprotectin. J Clin Lab Anal 2020; 34:e23059. [PMID: 31587371 PMCID: PMC7031577 DOI: 10.1002/jcla.23059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 09/18/2019] [Accepted: 09/21/2019] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Fecal calprotectin (FC) is widely used to discriminate between patients with inflammatory diseases such as inflammatory bowel disease (IBD) and functional diseases such as irritable bowel syndrome (IBS). ELISA is a time-consuming method for the measurement of FC, whereas a fluorescent immunochromatography test can obtain results in around 30 minutes and thus enables a rapid response to clinical decision. METHODS Two methods, the Proglead® calprotectin (FC Proglead) and the BÜHLMANN fCAL® ELISA (FC BÜHLMANN), were used to quantitatively examine FC in 111 stool samples. The comparison and bias estimation of both assays were assessed using CLSI EP09c protocol. RESULTS The two methods were highly correlated (rho = .96). Deming regression was employed to calculate the regression equation, with a slope of 1.01 and an intercept of -4.98 μg/g. The estimated median bias (FC Proglead - FC BÜHLMANN) was -4.19 μg/g with the 95% limits of agreement (-55.59 to 47.21 μg/g), and the estimated median percent bias was -8.71% with the 95% limits of agreement (-50.31% to 32.90%). There was 4.50% (5/111) of values outside the 95% limits of agreement. Percent biases at the FC cutoff values of 50 and 200 μg/g between both methods evaluated by Deming regression were 8.96% and 1.49%, respectively. The biases were all less than the acceptable standard (10%). And, 99.10% of FC results were in agreement between both methods (kappa = .99, P < .001). CONCLUSIONS FC Proglead may be used as a suitable alternative to FC BÜHLMANN for the disease activity assessment for patients with IBD, considering its convenience and shorter turnaround time.
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Affiliation(s)
- Runqing Li
- Laboratory Medicine Department, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Xiuying Zhao
- Laboratory Medicine Department, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jingxiao Dong
- Laboratory Medicine Department, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Dong Zhu
- Laboratory Medicine Department, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Tengjiao Wang
- Laboratory Medicine Department, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Song Yang
- Laboratory Medicine Department, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Zhipeng Zhao
- Laboratory Medicine Department, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Nan Xiao
- Laboratory Medicine Department, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
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Abstract
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by inflammatory cell infiltration, high levels of cytokines, and erosion of cartilage and bone in joints. Calprotectin (CLP), as a recently described member of S100 family proteins, is a heterodimeric complex of S100A8 and S100A9. Currently, plenty of studies have indicated significantly increased serum and synovial fluid levels of CLP in patients with RA. It was reported that CLP was related to cell differentiation, migration, apoptosis, and production of pro-inflammatory factors in RA. In addition, there are the positive relationships between serum, synovial CLP and traditional acute phase reactants, disease activity, ultrasound and radiographic progression of joints, and treatment response of RA. In this review, we mainly discuss the role of CLP in the pathogenesis of RA as well as its potential to estimate clinical disease progression of RA patients.
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Klingberg E, Magnusson MK, Strid H, Deminger A, Ståhl A, Sundin J, Simrén M, Carlsten H, Öhman L, Forsblad-d'Elia H. A distinct gut microbiota composition in patients with ankylosing spondylitis is associated with increased levels of fecal calprotectin. Arthritis Res Ther 2019; 21:248. [PMID: 31771630 PMCID: PMC6880506 DOI: 10.1186/s13075-019-2018-4] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 10/01/2019] [Indexed: 02/06/2023] Open
Abstract
Background Ankylosing spondylitis (AS) shares many characteristics with inflammatory bowel disease (IBD). Intestinal microbiota most likely plays an important role in the development of IBDs and may also be involved in the pathogenesis of AS. We aimed to define and compare the fecal microbiota composition in patients with AS, ulcerative colitis (UC), and healthy controls (HC) and to determine relationships between fecal microbiota, fecal calprotectin, and disease-related variables in AS. Methods Fecal microbiota composition was assessed with GA-map™ Dysbiosis Test (Genetic Analysis, Oslo, Norway), which also reports the degree of deviation of the microbiota composition compared with a healthy control population, a Dysbiosis Index (DI) score 1–5. The AS patients were assessed with questionnaires, back mobility tests, fecal calprotectin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results Totally, 150 patients with AS (55% men, median age 55.5 years, median BASDAI 3.2), 18 patients with UC (56% men, median age 30.5 years), and 17 HC (65% men, median age 22 years) were included. Principal component analysis showed highly separate clustering of fecal microbiota from the patients with AS, UC, and HC. Compared with HC, fecal microbiota in AS was characterized by a higher abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcus species, and Actinobacteria, but lower abundance of Bacteroides and Lachnospiraceae. Further, fecal microbiota composition differed between patients with normal (≤ 50 mg/kg, n = 57) and increased (≥ 200 mg/kg, n = 36) fecal calprotectin. Patients with increased fecal calprotectin had lower abundance of bacteria with anti-inflammatory properties such as Faecalibacterium prausnitzii and Clostridium and higher abundance of the genus Streptococcus. No association was found between the fecal microbiota composition and HLAB27 status, disease activity, function, or medication. Dysbiosis (defined as DI ≥ 3) was found in 87% of AS patients. Conclusions Patients with AS have a distinct fecal microbiota signature, which is linked to fecal calprotectin levels, a marker of intestinal inflammation, but not to other clinical parameters. These findings suggest a local interplay between intestinal microbiota and gut inflammation in AS. Trial registration ClinicalTrials.gov, NCT00858819. Registered March 9, 2009.
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Affiliation(s)
- Eva Klingberg
- Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. .,Department of Rheumatology, Sahlgrenska University Hospital, Gröna stråket 14, SE-41345, Gothenburg, Sweden.
| | - Maria K Magnusson
- Department of Microbiology and Immunology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Hans Strid
- Department of Internal Medicine, Södra Älvsborgs sjukhus, Borås, Sweden.,Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Anna Deminger
- Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Arne Ståhl
- Department of Microbiology and Immunology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Johanna Sundin
- Department of Microbiology and Immunology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.,Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Magnus Simrén
- Department of Microbiology and Immunology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.,Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Hans Carlsten
- Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Lena Öhman
- Department of Microbiology and Immunology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Helena Forsblad-d'Elia
- Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.,Department of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden
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Salem F, Kindt N, Marchesi JR, Netter P, Lopez A, Kokten T, Danese S, Jouzeau JY, Peyrin-Biroulet L, Moulin D. Gut microbiome in chronic rheumatic and inflammatory bowel diseases: Similarities and differences. United European Gastroenterol J 2019; 7:1008-1032. [PMID: 31662859 DOI: 10.1177/2050640619867555] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Accepted: 07/13/2019] [Indexed: 02/06/2023] Open
Abstract
Introduction Inflammatory bowel diseases (IBDs) and chronic rheumatic diseases (CRDs) are systemic chronic disorders sharing common genetic, immune and environmental factors. About half of patients with IBD develop rheumatic ailments and microscopic intestinal inflammation is present in up to half of CRD patients. IBD and CRD patients also share a common therapeutic armamentarium. Disequilibrium in the complex realm of microbes (known as dysbiosis) that closely interact with the gut mucosal immune system has been associated with both IBD and CRD (spondyloarthritis and rheumatoid arthritis). Whether dysbiosis represents an epiphenomenon or a prodromal feature remains to be determined. Methods In an attempt to further investigate whether specific gut dysbiosis may be the missing link between IBD and CRD in patients developing both diseases, we performed here a systematic literature review focusing on studies looking at bacterial microbiota in CRD and/or IBD patients. Results We included 80 studies, with a total of 3799 IBD patients without arthritis, 1084 CRD patients without IBD, 132 IBD patients with arthropathy manifestations and 12 spondyloarthritis patients with IBD history. Overall, this systematic review indicates that an increase in Bifidobacterium, Staphylococcus, Enterococcus, Lactobacillus, Pseudomonas, Klebsiella and Proteus genera, as well as a decrease in Faecalibacterium, Roseburia genera and species belonging to Verrucomicrobia and Fusobacteria phyla are common features in IBD and CRD patients, whereas dozens of bacterial species are specific features of CRD and IBD. Conclusion Further work is needed to understand the functions of bacteria and of their metabolites but also to characterize fungi and viruses that are commonly found in these patients.
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Affiliation(s)
- Fatouma Salem
- IMoPA, UMR7365 CNRS-Université de Lorraine, Vandœuvre Les Nancy, France
| | - Nadège Kindt
- IMoPA, UMR7365 CNRS-Université de Lorraine, Vandœuvre Les Nancy, France
| | - Julian R Marchesi
- Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, UK.,School of Biosciences, Museum Avenue, Cardiff University, UK
| | - Patrick Netter
- IMoPA, UMR7365 CNRS-Université de Lorraine, Vandœuvre Les Nancy, France
| | - Anthony Lopez
- NGERE, UMR_ U1256 INSERM-Université de Lorraine, Vandœuvre Les Nancy, France.,Service d'hépato-gastroentérologie, CHRU de Nancy, Vandœuvre Les Nancy, France
| | - Tunay Kokten
- NGERE, UMR_ U1256 INSERM-Université de Lorraine, Vandœuvre Les Nancy, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy
| | - Jean-Yves Jouzeau
- IMoPA, UMR7365 CNRS-Université de Lorraine, Vandœuvre Les Nancy, France
| | - Laurent Peyrin-Biroulet
- NGERE, UMR_ U1256 INSERM-Université de Lorraine, Vandœuvre Les Nancy, France.,Service d'hépato-gastroentérologie, CHRU de Nancy, Vandœuvre Les Nancy, France
| | - David Moulin
- IMoPA, UMR7365 CNRS-Université de Lorraine, Vandœuvre Les Nancy, France.,CHRU de Nancy, Contrat d'interface, Vandœuvre Les Nancy, France
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Biomarkers in Inflammatory Bowel Disease-Associated Spondyloarthritis: State of the Art and Unmet Needs. J Immunol Res 2019; 2019:8630871. [PMID: 31276001 PMCID: PMC6589275 DOI: 10.1155/2019/8630871] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Accepted: 05/27/2019] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease-associated spondyloarthritis is a systemic disease characterized by the chronic inflammation of both the gastrointestinal tract and the musculoskeletal system. Since inflammatory bowel disease-associated spondyloarthritis has been associated with a significant diagnostic delay, which may lead to poor quality of life and progression of joint damage, efforts to discover new reliable and noninvasive diagnostic biomarkers have been made. We reviewed the state of the art of biomarker research in inflammatory bowel disease-associated spondyloarthritis, showing that to date it has been largely unsatisfactory. Only a few of the biomarkers that have been investigated are likely to enter the clinical practice upon further validation in independent cohorts. The research of new and innovative biomarkers for inflammatory bowel disease-associated spondyloarthritis is warranted.
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49
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Hedin CRH, Vavricka SR, Stagg AJ, Schoepfer A, Raine T, Puig L, Pleyer U, Navarini A, van der Meulen-de Jong AE, Maul J, Katsanos K, Kagramanova A, Greuter T, González-Lama Y, van Gaalen F, Ellul P, Burisch J, Bettenworth D, Becker MD, Bamias G, Rieder F. The Pathogenesis of Extraintestinal Manifestations: Implications for IBD Research, Diagnosis, and Therapy. J Crohns Colitis 2019; 13:541-554. [PMID: 30445584 DOI: 10.1093/ecco-jcc/jjy191] [Citation(s) in RCA: 131] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
This article reports on the sixth scientific workshop of the European Crohn's and Colitis Organisation [ECCO] on the pathogenesis of extraintestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. This paper has been drafted by 15 ECCO members and 6 external experts [in rheumatology, dermatology, ophthalmology, and immunology] from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search, the supporting text was finalized under the leadership of the heads of the working groups before being integrated by the group consensus leaders.
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Affiliation(s)
- C R H Hedin
- Gastroenterology unit, Patient Area Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - S R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - A J Stagg
- Centre for Immunobiology, Bart's and The London Medical School, Queen Mary University of London, London, UK
| | - A Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
| | - T Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Teaching Hospitals NHS Foundation Trust, Cambridge, UK
| | - L Puig
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau. Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
| | - U Pleyer
- University Eye Clinic, Uveitis Center, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - A Navarini
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | | | - J Maul
- Gastroenterologie am Bayerischen Platz, Berlin, Germany
- Department of Medicine (Gastroenterology, Infectious Diseases, Rheumatology), Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - K Katsanos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Ioannina School of Medical Sciences, Ioannina, Greece
| | - A Kagramanova
- IBD Department, The Loginov Moscow Clinical Scientific Centre, Moscow, Russia
| | - T Greuter
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
- Gastroenterology Research Unit, Mayo Clinic, Rochester, MN, USA
| | - Y González-Lama
- IBD Unit, Gastroenterology and Hepatology Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - F van Gaalen
- Department of Rheumatology, Leiden University Medical Center [LUMC], Leiden, Netherlands
| | - P Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | - J Burisch
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
- Abdominal Center K, Medical Section, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - D Bettenworth
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - M D Becker
- Department of Ophthalmology, Triemli Hospital, Zurich, Switzerland & Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany
| | - G Bamias
- National and Kapodistrian University of Athens, GI Unit, 3rd Academic Department of Internal Medicine, Sotiria Hospital, Athens, Greece
| | - F Rieder
- Department of Gastroenterology, Hepatology and Nutrition; Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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50
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Simioni J, Skare TL, Campos APB, Kotze L, Messias-Reason I, Ioshii SO, Nisihara R. Fecal Calprotectin, Gut Inflammation and Spondyloarthritis. Arch Med Res 2019; 50:41-46. [PMID: 31101242 DOI: 10.1016/j.arcmed.2019.04.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 04/12/2019] [Indexed: 01/18/2023]
Abstract
BACKGROUND Gut inflammation is closely related to spondyloarthritis (SpA) pathophysiology. Fecal calprotectin has been used to measure the degree of gut inflammation. The phenotype of SpA may change according to studied population. AIM To study the fecal calprotectin levels in a sample of SpA in Brazilian patients and its relationship with epidemiological, clinical and treatment variables as well as with the macro and microscopic degree of gut inflammation. METHODS Eighty five SpA patients were studied for epidemiological and clinical features, functional and inflammatory indexes and fecal calprotectin levels measured using a ELISA kit. Colonoscopy with intestinal biopsies were performed in 39 of them. At time of colonoscopy a second calprotectin level was done after suspension of at least 3 weeks of used anti-inflammatory nonsteroidal drugs (NSAIDs). RESULTS Fecal calprotectin levels were higher in Ankylosing Spondylitis (AS) patients (p <0.0001) and in those with axial involvement (p = 0.002). No relationship was found with SpA inflammatory and functional parameters (all p = ns). After suspension of NSAIDs, a drop in fecal calprotectin levels was observed (from median levels of 215.0-76.0 μg/g; p = 0.01). In the colonoscopy, 33.3% had macroscopic signs of inflammation and these patients had higher calprotectin (p = 0.009) than others. Microscopic examination showed that all patients had lymphoplasmacytic infiltrate and eosinophilic infiltrate; epithelial erosion was present in 27.2%. CONCLUSIONS Patients with ankylosing spondylitis and axial forms of diseases have higher fecal calprotectin levels. Patients with all types of SpA have microscopic inflammatory changes in the gut.
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Affiliation(s)
- Juliana Simioni
- Rheumatology Unit, Evangelical University Mackenzie of Paraná, Curitiba, Paraná, Brazil; Internal Medicine Post Graduate, Clinical Hospital, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Thelma L Skare
- Rheumatology Unit, Evangelical University Mackenzie of Paraná, Curitiba, Paraná, Brazil
| | - Ana Paula B Campos
- Rheumatology Unit, Evangelical University Mackenzie of Paraná, Curitiba, Paraná, Brazil
| | - Lorete Kotze
- Internal Medicine Post Graduate, Clinical Hospital, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Iara Messias-Reason
- Internal Medicine Post Graduate, Clinical Hospital, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Sergio O Ioshii
- Division of Pathology, Federal University of Paraná, Postgraduate Program in Technology in Health, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil
| | - Renato Nisihara
- Rheumatology Unit, Evangelical University Mackenzie of Paraná, Curitiba, Paraná, Brazil; Internal Medicine Post Graduate, Clinical Hospital, Federal University of Paraná, Curitiba, Paraná, Brazil; Department of Medicine, Positivo University, Curitiba, Paraná, Brazil.
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