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Westfall KM, Charles R, Steinhagen E. Diagnosis and Differentiation of Inflammatory Bowel Disease. Surg Clin North Am 2025; 105:217-232. [PMID: 40015813 DOI: 10.1016/j.suc.2024.09.005] [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] [Indexed: 03/01/2025]
Abstract
Differentiating Crohn's disease from ulcerative colitis may be a diagnostic challenge for clinicians due to overlapping features. However, the correct diagnosis may guide treatment options and considerations regarding surgery. This study reviews the common components of diagnostic evaluation of inflammatory bowel disease. Additionally, this article provides a basis of understanding for the more complex aspects of the disease to be discussed in subsequent studies.
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Affiliation(s)
- Kristen M Westfall
- Department of Surgery, Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Ronald Charles
- Department of Surgery, Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Emily Steinhagen
- Department of Surgery, Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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Tomašić V, Bišćanin A, Kralj D, Ćaćić P, Ogresta D. Non-Invasive Methods of Diagnosis and Management of Patients with Ulcerative Colitis. UNVEILING ULCERATIVE COLITIS - A COMPREHENSIVE APPROACH TO UNDERSTANDING AND MANAGEMENT 2024. [DOI: 10.5772/intechopen.1007643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2025]
Abstract
The global incidence and age-standardized prevalence rate of ulcerative colitis (UC) is increasing worldwide. It is a debilitating and lifelong inflammatory disease affecting both pediatric and adult patients. Thus, it is important to focus on modern treat-to-target approach, based on a tight control of the disease with close monitoring through interval assessments and modification of the treatment. Endoscopy remains the key method for UC assessment, but recent guidelines focus on implementation of non-invasive methods for UC diagnosis and management such as biomarkers (C-reactive protein, fecal calprotectin, and fecal lactofferin) and imaging methods (intestinal ultrasound). We summarize the diagnostic performance of non-invasive tests and present current evidence-based non-invasive strategy recommendations for UC monitoring.
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Ghozzi M, Mankai A, Mechi F, Ben Chedly Z, Kallala O, Melayah S, Trabelsi A, Ghedira I. High frequency of anti-Saccharomyces cerevisiae antibodies in chronic hepatitis C. Arab J Gastroenterol 2024; 25:378-382. [PMID: 39289081 DOI: 10.1016/j.ajg.2024.07.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 07/16/2024] [Accepted: 07/26/2024] [Indexed: 09/19/2024]
Abstract
BACKGROUND AND STUDY AIM Chronic hepatitis C (CHC) is a liver disease caused by the hepatitis C virus. Anti-Saccharomyces cerevisiae (S. cerevisiae) antibodies (ASCA) are frequently reported in autoimmune diseases but rarely in viral infections. We aimed to determine the frequency of ASCA in adult patients with CHC. PATIENTS AND METHODS Eighty-eight patients with CHC and 160 healthy blood donors were included in this study. ASCA-IgG and IgA levels were determined using enzyme linked immunosorbent assay. For statistical analysis, we used open EPI version 3 as software. Correlations were determined by Spearman's test using IBM® SPSS® Statistics. RESULTS ASCA (IgG or IgA) were present in 31.8 % of patients and in 3.7 % of controls (p < 10-6). ASCA-IgG and ASCA-IgA were more frequent in patients with CHC than in healthy subjects (23.9 % vs. 3.1 %; p < 10-5 and 9.1 % vs. 0.6 %; p = 0.002, respectively). In patients, mean levels of ASCA-IgG and IgA were significantly higher than in controls (9.95 ± 11.78 U/mL vs. 2.28 ± 2.86 U/mL, p < 10-6 and 5.96 ± 7.69 U/mL vs. 0.56 ± 0.12 U/mL, p < 10-6; respectively). In patients with CHC, the mean level of ASCA-IgG was significantly higher than that of ASCA-IgA (9.95 ± 11.78 U/mL vs. 5.96 ± 7.69 U/mL, p = 0.008). CONCLUSION The frequency of ASCA was significantly higher in patients with CHC than in healthy controls.
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Affiliation(s)
- Mariam Ghozzi
- Department of Immunology, Faculty of Pharmacy, Monastir University, Monastir, Tunisia; Laboratory of Immunology, Farhat Hached Hospital, Sousse, Tunisia; Research Unit "Epidemiology and Immunogenetics of Viral Infections, LR14SP02", Sahloul University Hospital, Sousse, Tunisia.
| | - Amani Mankai
- High School of Sciences and Techniques of Health, Tunis El Manar University, Tunis, Tunisia; Research Unit "Obesity: Etiopathology and Treatment, UR18ES01", National Institute of Nutrition and Food Technology, Tunis, Tunisia
| | - Fatma Mechi
- Department of Immunology, Faculty of Pharmacy, Monastir University, Monastir, Tunisia
| | - Zeineb Ben Chedly
- Department of Immunology, Faculty of Pharmacy, Monastir University, Monastir, Tunisia
| | - Ouafa Kallala
- Research Unit "Epidemiology and Immunogenetics of Viral Infections, LR14SP02", Sahloul University Hospital, Sousse, Tunisia; Laboratory of Microbiology, Sahloul University Hospital, Sousse, Tunisia; Department of Microbiology, Faculty of Pharmacy, Monastir University, Monastir, Tunisia
| | - Sarra Melayah
- Department of Immunology, Faculty of Pharmacy, Monastir University, Monastir, Tunisia; Laboratory of Immunology, Farhat Hached Hospital, Sousse, Tunisia; LR12SP11, Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia
| | - Abdelhalim Trabelsi
- Research Unit "Epidemiology and Immunogenetics of Viral Infections, LR14SP02", Sahloul University Hospital, Sousse, Tunisia; Laboratory of Microbiology, Sahloul University Hospital, Sousse, Tunisia; Department of Microbiology, Faculty of Pharmacy, Monastir University, Monastir, Tunisia
| | - Ibtissem Ghedira
- Department of Immunology, Faculty of Pharmacy, Monastir University, Monastir, Tunisia; Laboratory of Immunology, Farhat Hached Hospital, Sousse, Tunisia
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Li F, Wang Z, Tang T, Zhao Q, Wang Z, Han X, Xu Z, Chang Y, Li H, Hu S, Yu C, Chang S, Liu Y, Li Y. From serum metabolites to the gut: revealing metabolic clues to susceptibility to subtypes of Crohn's disease and ulcerative colitis. Front Endocrinol (Lausanne) 2024; 15:1375896. [PMID: 39175573 PMCID: PMC11338916 DOI: 10.3389/fendo.2024.1375896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 07/23/2024] [Indexed: 08/24/2024] Open
Abstract
Background and aims Inflammatory bowel disease (IBD) is a common chronic inflammatory bowel disease characterized by diarrhea and abdominal pain. Recently human metabolites have been found to help explain the underlying biological mechanisms of diseases of the intestinal system, so we aimed to assess the causal relationship between human blood metabolites and susceptibility to IBD subtypes. Methods We selected a genome-wide association study (GWAS) of 275 metabolites as the exposure factor, and the GWAS dataset of 10 IBD subtypes as the outcome, followed by univariate and multivariate analyses using a two-sample Mendelian randomization study (MR) to study the causal relationship between exposure and outcome, respectively. A series of sensitivity analyses were also performed to ensure the robustness of the results. Results A total of 107 metabolites were found to be causally associated on univariate analysis after correcting for false discovery rate (FDR), and a total of 9 metabolites were found to be significantly causally associated on subsequent multivariate and sensitivity analyses. In addition we found causal associations between 7 metabolite pathways and 6 IBD subtypes. Conclusion Our study confirms that blood metabolites and certain metabolic pathways are causally associated with the development of IBD subtypes and their parenteral manifestations. The exploration of the mechanisms of novel blood metabolites on IBD may provide new therapeutic ideas for IBD patients.
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Affiliation(s)
- Fan Li
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Zhaodi Wang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Tongyu Tang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Qi Zhao
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Zhi Wang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Xiaoping Han
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Zifeng Xu
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Yu Chang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Hongyan Li
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Sileng Hu
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Chanjiao Yu
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Shiyu Chang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Yue Liu
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
| | - Yuqin Li
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center, Jilin University, Changchun, China
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Lee SH, Shin M, Kim SH, Kim SP, Yoon HJ, Park Y, Koh J, Oh SH, Ko JS, Moon JS, Kim KM. Prevalence of Inflammatory Bowel Disease Unclassified, as Estimated Using the Revised Porto Criteria, among Korean Pediatric Patients with Inflammatory Bowel Disease. Pediatr Gastroenterol Hepatol Nutr 2024; 27:206-214. [PMID: 39035400 PMCID: PMC11254648 DOI: 10.5223/pghn.2024.27.4.206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 05/06/2024] [Indexed: 07/23/2024] Open
Abstract
Purpose Few studies have reported the prevalence of inflammatory bowel disease unclassified (IBDU) among Korean pediatric IBD (PIBD) population. To address this gap, we used two tertiary centers and nationwide population-based healthcare administrative data to estimate the prevalence of Korean pediatric IBDU at the time of diagnosis. Methods We identified 136 patients aged 2-17 years with newly diagnosed IBD (94 Crohn's disease [CD] and 42 ulcerative colitis [UC]) from two tertiary centers in Korea between 2005 and 2017. We reclassified these 136 patients using the revised Porto criteria. To estimate the population-based prevalence, we analyzed Korean administrative healthcare data between 2005 and 2016, which revealed 3,650 IBD patients, including 2,538 CD and 1,112 UC. By extrapolating the reclassified results to a population-based dataset, we estimated the prevalence of PIBD subtypes. Results Among the 94 CD, the original diagnosis remained unchanged in 93 (98.9%), while the diagnosis of one (1.1%) patient was changed to IBDU. Among the 42 UC, the original diagnosis remained unchanged in 13 (31.0%), while the diagnoses in 11 (26.2%), 17 (40.5%), and one (2.4%) patient changed to atypical UC, IBDU, and CD, respectively. The estimated prevalences of CD, UC, atypical UC, and IBDU in the Korean population were 69.5%, 9.4%, 8.0%, and 13.1%, respectively. Conclusion This study is the first in Korea to estimate the prevalence of pediatric IBDU. This prevalence (13.1%) aligns with findings from Western studies. Large-scale prospective multicenter studies on PIBDU are required to examine the clinical features and outcomes of this condition.
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Affiliation(s)
- Sung Hee Lee
- Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Minsoo Shin
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Seo Hee Kim
- Department of Pediatrics, Chonnam National University Children’s Hospital, Chonnam National University College of Medicine, Gwangju, Korea
| | - Seong Pyo Kim
- Interdisciplinary Program of Medical Informatics, Seoul National University College of Medicine, Seoul, Korea
| | - Hyung-Jin Yoon
- Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, Korea
| | - Yangsoon Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jaemoon Koh
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Seak Hee Oh
- Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Sung Ko
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jin Soo Moon
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung Mo Kim
- Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea
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Vălean D, Zaharie R, Țaulean R, Usatiuc L, Zaharie F. Recent Trends in Non-Invasive Methods of Diagnosis and Evaluation of Inflammatory Bowel Disease: A Short Review. Int J Mol Sci 2024; 25:2077. [PMID: 38396754 PMCID: PMC10889152 DOI: 10.3390/ijms25042077] [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: 01/16/2024] [Revised: 02/04/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Inflammatory bowel diseases are a conglomerate of disorders causing inflammation of the gastrointestinal tract, which have gained a significant increase in prevalence in the 21st century. As they present a challenge in the terms of diagnosis as well as treatment, IBDs can present an overwhelming impact on the individual and can take a toll on healthcare costs. Thus, a quick and precise diagnosis is required in order to prevent the high number of complications that can arise from a late diagnosis as well as a misdiagnosis. Although endoscopy remains the primary method of evaluation for IBD, recent trends have highlighted various non-invasive methods of diagnosis as well as reevaluating previous ones. This review focused on the current non-invasive methods in the diagnosis of IBD, exploring their possible implementation in the near future, with the goal of achieving earlier, feasible, and cheap methods of diagnosis as well as prognosis in IBD.
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Affiliation(s)
- Dan Vălean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roxana Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of Gastroenterology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roman Țaulean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Lia Usatiuc
- Department of Patophysiology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania;
| | - Florin Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
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Sendid B, Cornu M, Cordier C, Bouckaert J, Colombel JF, Poulain D. From ASCA breakthrough in Crohn's disease and Candida albicans research to thirty years of investigations about their meaning in human health. Autoimmun Rev 2024; 23:103486. [PMID: 38040100 DOI: 10.1016/j.autrev.2023.103486] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 11/23/2023] [Indexed: 12/03/2023]
Abstract
Anti-Saccharomyces cerevisiae antibodies (ASCA) are human antibodies that can be detected using an enzyme-linked immunosorbent assay involving a mannose polymer (mannan) extracted from the cell wall of the yeast S. cerevisiae. The ASCA test was developed in 1993 with the aim of differentiating the serological response in two forms of inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis. The test, which is based on the detection of anti-oligomannosidic antibodies, has been extensively performed worldwide and there have been hundreds of publications on ASCA. The earlier studies concerned the initial diagnostic indications of ASCA and investigations then extended to many human diseases, generally in association with studies on intestinal microorganisms and the interaction of the micro-mycobiome with the immune system. The more information accumulates, the more the mystery of the meaning of ASCA deepens. Many fundamental questions remain unanswered. These questions concern the heterogeneity of ASCA, the mechanisms of their generation and persistence, the existence of self-antigens, and the relationship between ASCA and inflammation and autoimmunity. This review aims to discuss the gray areas concerning the origin of ASCA from an analysis of the literature. Structured around glycobiology and the mannosylated antigens of S. cerevisiae and Candida albicans, this review will address these questions and will try to clarify some lines of thought. The importance of the questions relating to the pathophysiological significance of ASCA goes far beyond IBD, even though these diseases remain the preferred models for their understanding.
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Affiliation(s)
- Boualem Sendid
- INSERM U1285, CNRS UMR 8576, Glycobiology in Fungal Pathogenesis and Clinical Applications, Université de Lille, F-59000 Lille, France; Pôle de Biologie-Pathologie-Génétique, Institut de Microbiologie, Service de Parasitologie-Mycologie, CHU Lille, F-59000 Lille, France.
| | - Marjorie Cornu
- INSERM U1285, CNRS UMR 8576, Glycobiology in Fungal Pathogenesis and Clinical Applications, Université de Lille, F-59000 Lille, France; Pôle de Biologie-Pathologie-Génétique, Institut de Microbiologie, Service de Parasitologie-Mycologie, CHU Lille, F-59000 Lille, France
| | - Camille Cordier
- INSERM U1285, CNRS UMR 8576, Glycobiology in Fungal Pathogenesis and Clinical Applications, Université de Lille, F-59000 Lille, France; Pôle de Biologie-Pathologie-Génétique, Institut de Microbiologie, Service de Parasitologie-Mycologie, CHU Lille, F-59000 Lille, France
| | - Julie Bouckaert
- CNRS UMR 8576, Computational Molecular Systems Biology, Université de Lille, F-59000 Lille, France
| | - Jean Frederic Colombel
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Daniel Poulain
- INSERM U1285, CNRS UMR 8576, Glycobiology in Fungal Pathogenesis and Clinical Applications, Université de Lille, F-59000 Lille, France.
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Liu R, Li D, Haritunians T, Ruan Y, Daly MJ, Huang H, McGovern DP. Profiling the inflammatory bowel diseases using genetics, serum biomarkers, and smoking information. iScience 2023; 26:108053. [PMID: 37841595 PMCID: PMC10568094 DOI: 10.1016/j.isci.2023.108053] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 07/28/2023] [Accepted: 09/22/2023] [Indexed: 10/17/2023] Open
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) are two etiologically related yet distinctive subtypes of the inflammatory bowel diseases (IBD). Differentiating CD from UC can be challenging using conventional clinical approaches in a subset of patients. We designed and evaluated a novel molecular-based prediction model aggregating genetics, serum biomarkers, and tobacco smoking information to assist the diagnosis of CD and UC in over 30,000 samples. A joint model combining genetics, serum biomarkers and smoking explains 46% (42-50%, 95% CI) of phenotypic variation. Despite modest overlaps with serum biomarkers, genetics makes unique contributions to distinguishing IBD subtypes. Smoking status only explains 1% (0-6%, 95% CI) of the phenotypic variance suggesting it may not be an effective biomarker. This study reveals that molecular-based models combining genetics, serum biomarkers, and smoking information could complement current diagnostic strategies and help classify patients based on biologic state rather than imperfect clinical parameters.
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Affiliation(s)
- Ruize Liu
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Dalin Li
- F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Talin Haritunians
- F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Yunfeng Ruan
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Mark J. Daly
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Hailiang Huang
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Dermot P.B. McGovern
- F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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Vera Chamorro JF, Sánchez Franco C, Vargas Sandoval M, Mora Quintero DV, Riveros López JP, Sarmiento Quintero F, Ortiz-Piedrahita C, Calderón-Guerrero OG, Laignelet H, Losada Gómez CL, Sánchez DP, López Panqueva RDP, Aponte Barrios W, Triana Rodríguez GA, Osorno A, Becerra Granados LM, Ortega López MC, Correa Jiménez Ó, Maradei Anaya SJ, García Acero M, Acevedo Forero AM, Prada A, Ramírez Urrego LC, Salcedo Castilla LK, Enríquez A, Suárez Fuentes MA, González Leal N, Peña Hernández S, Sotaquirá Guáqueta L, Sosa F, Fierro F, Correa S, Martín de Carpi FJ. Consenso colombiano de la enfermedad inflamatoria intestinal pediátrica. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2023; 38:1-75. [DOI: 10.22516/25007440.943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Introducción: la colitis ulcerativa pediátrica (CUP), la enfermedad de Crohn pediátrica (ECP) y la enfermedad inflamatoria intestinal pediátrica no clasificable (EIIPNC) tienen particularidades clínicas y psicosociales que las diferencian de las del adulto y pueden condicionar enfoques terapéuticos distintos por las posibles repercusiones nutricionales, crecimiento y desarrollo, lo que representa un desafío para el pediatra y el gastroenterólogo. Objetivo: desarrollar recomendaciones basadas en la evidencia por consenso de expertos para el diagnóstico y el tratamiento oportunos y seguros de la enfermedad inflamatoria intestinal pediátrica (EIIP) en menores de 18 años, para los profesionales que atienden estos pacientes y los pagadores en salud. Metodología: a través de un panel de expertos del Colegio Colombiano de Gastroenterología, Hepatología y Nutrición Pediátrica (COLGAHNP) y un grupo multidisciplinario se formularon 35 preguntas en relación con el cuadro clínico, el diagnóstico y el tratamiento de la EIIP. A través de una revisión y un análisis crítico de la literatura, con especial énfasis en las principales guías de práctica clínica (GPC), estudios clínicos aleatorizados (ECA) y metaanálisis de los últimos 10 años, los expertos plantearon 77 recomendaciones que respondían a cada una de las preguntas de investigación con sus respectivos puntos prácticos. Posteriormente, cada una de las afirmaciones se sometieron a votación dentro del grupo desarrollador, incluyendo las afirmaciones que alcanzaron > 80 %. Resultados: todas las afirmaciones alcanzaron una votación > 80 %. La EIIP tiene mayor extensión, severidad y evolución hacia la estenosis, enfermedad perianal, manifestaciones extraintestinales y retraso en el crecimiento en comparación con los pacientes adultos, por lo que su manejo debe ser realizado por grupos multidisciplinarios liderados por gastroenterólogos pediatras y prepararlos para una transición a la edad adulta. Los criterios de Porto permiten una clasificación práctica de la EIIP. En la ECP, debemos usar la clasificación de París y debemos realizar ileocolonoscopia y esofagogastroduodenoscopia, ya que el 50 % tienen un compromiso superior, usando el SES-CD (UCEIS/Mayo en CUP) y tomando múltiples biopsias. Los laboratorios iniciales deben incluir marcadores de inflamación, calprotectina fecal y descartar infecciones intestinales. El tratamiento, la inducción y el mantenimiento de la EIIP deben ser individualizados y decididos según la estratificación de riesgo. En el seguimiento se debe usar el Pediatric Crohn Disease Activity Index (PCDAI) y Pediatric Ulcerative Colitis Activity Index (PUCAI) de las últimas 48 horas. Los pacientes con EIIP temprana e infantil, deben ser valorados por inmunólogos y genetistas. Conclusión: se proporciona una guía de consenso con recomendaciones basadas en la evidencia sobre el diagnóstico y los tratamientos oportunos y seguros en los pacientes con EIIP.
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Sokollik C, Pahud de Mortanges A, Leichtle AB, Juillerat P, Horn MP. Machine Learning in Antibody Diagnostics for Inflammatory Bowel Disease Subtype Classification. Diagnostics (Basel) 2023; 13:2491. [PMID: 37568854 PMCID: PMC10417520 DOI: 10.3390/diagnostics13152491] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 07/21/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
Antibody testing in inflammatory bowel disease (IBD) can add to diagnostic accuracy of the main subtypes Crohn's disease (CD) and ulcerative colitis (UC). Whether modern modeling techniques such as supervised and unsupervised machine learning are of value for finer distinction of subtypes such as IBD-unclassified (IBD-U) is not known. We determined the antibody profile of 100 adult IBD patients from the Swiss IBD cohort study with known subtype (50 CD, 50 UC) as well as of 76 IBD-U patients. We included ASCA IgG and IgA, p-ANCA, MPO- and PR3-ANCA, and xANCA measurements for computing different antibody panels as well as machine learning models. The AUC of an optimized antibody panel was 85% (95%CI, 78-92%) to distinguish CD from UC patients. The antibody profile of IBD-U patients was closely related to UC. No specific antibody profile was predictive for IBD-U nor for re-classification. The panel diagnostic was in favor of UC reclassification prediction with a correct assignment rate of 69.2-73.1% depending on the cut-off applied. Supervised machine learning could not distinguish between CD, UC, and IBD-U. More so, unsupervised machine learning suggested only two distinct clusters as a likely number of IBD subtypes. Antibodies in IBD are supportive in confirming clinical determined subtypes CD and UC but have limited capacity to predict IBD-U and reclassification during follow-up. In terms of antibody profiles, IBD-U is not a distinct subtype of IBD.
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Affiliation(s)
- Christiane Sokollik
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University Children’s Hospital, Inselspital, University of Bern, 3010 Bern, Switzerland;
| | | | - Alexander B. Leichtle
- Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland;
- Center for Artificial Intelligence in Medicine (CAIM), University of Bern, 3010 Bern, Switzerland
| | - Pascal Juillerat
- Department of Gastroenterology, Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland;
- Crohn’s and Colitis Center, Gastroenterology Beaulieu SA, 1004 Lausanne, Switzerland
| | - Michael P. Horn
- Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland;
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Kathrani A, Theelen B, Bond R. Isolation of Malassezia yeasts from dogs with gastrointestinal disease undergoing duodenal endoscopy. J Small Anim Pract 2023. [PMID: 37681754 DOI: 10.1111/jsap.13649] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/03/2023] [Accepted: 06/08/2023] [Indexed: 09/09/2023]
Abstract
OBJECTIVES To culture Malassezia and other fungi from the duodenum of dogs with gastrointestinal signs undergoing routine endoscopic examination. MATERIALS AND METHODS Quantitative microbial culture was performed on duodenal juice aspirated from dogs with suspected enteropathy during routine upper gastrointestinal endoscopy; samples were cultured on Sabouraud's dextrose agar (30, 32 and 37°C) and modified Dixon agar (32°C) for 14 days. Isolates were identified phenotypically and by matrix-assisted laser desorption ionisation-time of flight, and internal transcribed spacer sequencing. Yeast presence was also evaluated by cytological and histopathological examination of smears and biopsy specimens. RESULTS Forty-five dogs were recruited with chronic inflammatory enteropathy (n=38), granulomatous colitis (n=2), gastric adenocarcinoma (n=2), duodenal small cell lymphoma (n=1) and idiopathic severe gastrointestinal haemorrhage (n=2). Fungi were cultured from 14 dogs: Malassezia pachydermatis was isolated from eight [chronic inflammatory enteropathy (n=7) (along with Candida albicans n=1); granulomatous colitis (n=1)] and Malassezia sympodialis from another (gastric adenocarcinoma). Five dogs with chronic inflammatory enteropathy yielded other yeasts (C. albicans, Candida glabrata, Kazachstania slooffiae, Kazachstania telluris, Pichia kudriavzevii [syn. C. krusei]). Yeasts were never observed in histopathological specimens. Fluorescent microscopical examination of cytological specimens showed yeast in only one case, from which K. slooffiae was subsequently isolated. CLINICAL SIGNIFICANCE Based on a literature search, this is the first report of isolation of M. pachydermatis, M. sympodialis, K. slooffiae and K. telluris from the canine duodenum. Further studies are needed to determine whether these are resident or transient fungi in the canine duodenum and whether their presence has a pathogenic effect on the host.
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Affiliation(s)
- A Kathrani
- Clinical Science and Services, Royal Veterinary College, North Mymms, Hatfield, AL9 7TA, UK
| | - B Theelen
- Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
| | - R Bond
- Clinical Science and Services, Royal Veterinary College, North Mymms, Hatfield, AL9 7TA, UK
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Sun M, Ju J, Xu H, Wang Y. Intestinal fungi and antifungal secretory immunoglobulin A in Crohn's disease. Front Immunol 2023; 14:1177504. [PMID: 37359518 PMCID: PMC10285161 DOI: 10.3389/fimmu.2023.1177504] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/30/2023] [Indexed: 06/28/2023] Open
Abstract
The human gastrointestinal tract harbors trillions of commensal microorganisms. Emerging evidence points to a possible link between intestinal fungal dysbiosis and antifungal mucosal immunity in inflammatory bowel disease, especially in Crohn's disease (CD). As a protective factor for the gut mucosa, secretory immunoglobulin A (SIgA) prevents bacteria from invading the intestinal epithelium and maintains a healthy microbiota community. In recent years, the roles of antifungal SIgA antibodies in mucosal immunity, including the regulation of intestinal immunity binding to hyphae-associated virulence factors, are becoming increasingly recognized. Here we review the current knowledge on intestinal fungal dysbiosis and antifungal mucosal immunity in healthy individuals and in patients with CD, discuss the factors governing antifungal SIgA responses in the intestinal mucosa in the latter group, and highlight potential antifungal vaccines targeting SIgA to prevent CD.
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13
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Burisch J. Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort. APMIS 2023; 131 Suppl 147:1-46. [PMID: 37336790 DOI: 10.1111/apm.13334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
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14
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Gergely M, Deepak P. Tools for the Diagnosis and Management of Crohn's Disease. Gastroenterol Clin North Am 2022; 51:213-239. [PMID: 35595412 DOI: 10.1016/j.gtc.2021.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Numerous tools have emerged over recent decades to aid in the increasingly complex management of patients with Crohn's disease (CD) beyond endoscopy, including video capsule endoscopy, magnetic resonance enterography, computed tomography enterography, a variety of biomarkers, and even wearable biosensors and smartphone applications. These tools have allowed for a more sophisticated and less invasive complementary approach to the evaluation of disease activity and treatment response in patients with CD. This article details the characteristics, practical application, and limitations of these various modalities and discusses how updated guidelines are now incorporating many of them into a treat-to-target strategy.
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Affiliation(s)
- Maté Gergely
- Division of Gastroenterology, Inflammatory Bowel Diseases Center, Washington University School of Medicine, 600 South Euclid Avenue, Campus Box 8124, Saint Louis, MO 63110, USA
| | - Parakkal Deepak
- Division of Gastroenterology, Inflammatory Bowel Diseases Center, Washington University School of Medicine, 600 South Euclid Avenue, Campus Box 8124, Saint Louis, MO 63110, USA.
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Li M, Zhang R, Li J, Li J. The Role of C-Type Lectin Receptor Signaling in the Intestinal Microbiota-Inflammation-Cancer Axis. Front Immunol 2022; 13:894445. [PMID: 35619716 PMCID: PMC9127077 DOI: 10.3389/fimmu.2022.894445] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 04/04/2022] [Indexed: 12/13/2022] Open
Abstract
As a subset of pattern recognition receptors (PRRs), C-type lectin-like receptors (CLRs) are mainly expressed by myeloid cells as both transmembrane and soluble forms. CLRs recognize not only pathogen associated molecular patterns (PAMPs), but also damage-associated molecular patterns (DAMPs) to promote innate immune responses and affect adaptive immune responses. Upon engagement by PAMPs or DAMPs, CLR signaling initiates various biological activities in vivo, such as cytokine secretion and immune cell recruitment. Recently, several CLRs have been implicated as contributory to the pathogenesis of intestinal inflammation, which represents a prominent risk factor for colorectal cancer (CRC). CLRs function as an interface among microbiota, intestinal epithelial barrier and immune system, so we firstly discussed the relationship between dysbiosis caused by microbiota alteration and inflammatory bowel disease (IBD), then focused on the role of CLRs signaling in pathogenesis of IBD (including Mincle, Dectin-3, Dectin-1, DCIR, DC-SIGN, LOX-1 and their downstream CARD9). Given that CLRs mediate intricate inflammatory signals and inflammation plays a significant role in tumorigenesis, we finally highlight the specific effects of CLRs on CRC, especially colitis-associated cancer (CAC), hoping to open new horizons on pathogenesis and therapeutics of IBD and CAC.
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Affiliation(s)
- Muhan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Runfeng Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingnan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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16
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Bourgonje AR, Vogl T, Segal E, Weersma RK. Antibody signatures in inflammatory bowel disease: current developments and future applications. Trends Mol Med 2022; 28:693-705. [DOI: 10.1016/j.molmed.2022.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/01/2022] [Accepted: 05/03/2022] [Indexed: 11/25/2022]
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Wei Y, Chen T, Yang W, Li H, Fang C, Liu Q, Chen Y, Mei Q. Detection of a novel antigen for Crohn's disease. Scand J Gastroenterol 2021; 56:1427-1433. [PMID: 34487462 DOI: 10.1080/00365521.2021.1973088] [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] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease (IBD). We identify an antigen-like substance called Crohn's disease (CD) antibody binding polypeptide (CABP). As a serological marker, anti-CABP may contribute to the diagnosis of IBD. The present study aims to evaluate the clinical role of anti-CABP as a serological antibody for IBD. METHODS Using enzyme-linked immunosorbent assay (ELISA), serum anti-CABP, anti-Saccharomyces cerevisiae antibody (ASCA) and perinuclear anti-neutrophil cytoplasmic antibody (pANCA), titers were tested in 168 CD patients, 123 ulcerative colitis (UC) patients and 170 controls. The correlation between serum antibody and clinical characteristics was investigated. The diagnostic potential of the anti-CABP was evaluated by receiver operating characteristic (ROC) analysis. RESULTS The titers of anti-CABP (IgA or IgG) and ASCA IgG of CD patients were significantly higher than non-CD group (all p < .01). In the differential diagnosis of CD and non-CD, anti-CABP IgA revealed an area under the curve (AUC) of 0.706 and anti-CABP IgG demonstrated an AUC of 0.788. As an individual antibody, anti-CABP could effectively distinguish CD from non-CD (AUC 0.816), and the diagnostic efficacy was better than that of ASCA (AUC 0.680). The combined use of anti-CABP, ASCA and pANCA significantly improved the diagnostic value (AUC 0.857). Anti-CABP positive rates were associated with perianal lesions and disease location in CD patients (both p < .05). CONCLUSIONS Our results suggested that anti-CABP could be used as a serological marker to assist the diagnosis of CD. CLINICAL TRIAL REGISTRATION This trial is registered with clinical trial registration unique identifier ChiCTR2000037094.
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Affiliation(s)
- Yarong Wei
- Department of Gastroenterology, the Key Laboratory of Digestive Diseases of Anhui Province, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | | | - Wu Yang
- Shanxi Ruihao Biotechnology Co. LTD, Taiyuan, China
| | - Huihui Li
- Department of Gastroenterology, the Key Laboratory of Digestive Diseases of Anhui Province, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Chen Fang
- Department of Gastroenterology, the Key Laboratory of Digestive Diseases of Anhui Province, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qiuyuan Liu
- Department of Gastroenterology, the Key Laboratory of Digestive Diseases of Anhui Province, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yonghao Chen
- Department of Gastroenterology, the Key Laboratory of Digestive Diseases of Anhui Province, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qiao Mei
- Department of Gastroenterology, the Key Laboratory of Digestive Diseases of Anhui Province, the First Affiliated Hospital of Anhui Medical University, Hefei, China
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Association of Fungi and Archaea of the Gut Microbiota with Crohn's Disease in Pediatric Patients-Pilot Study. Pathogens 2021; 10:pathogens10091119. [PMID: 34578152 PMCID: PMC8468012 DOI: 10.3390/pathogens10091119] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 08/29/2021] [Accepted: 08/29/2021] [Indexed: 01/10/2023] Open
Abstract
The composition of bacteria is often altered in Crohn’s disease (CD), but its connection to the disease is not fully understood. Gut archaea and fungi have recently been suggested to play a role as well. In our study, the presence and number of selected species of fungi and archaea in pediatric patients with CD and healthy controls were evaluated. Stool samples were collected from children with active CD (n = 54), non-active CD (n = 37) and control subjects (n = 33). The prevalence and the number of selected microorganisms were assessed by real-time PCR. The prevalence of Candida tropicalis was significantly increased in active CD compared to non-active CD and the control group (p = 0.011 and p = 0.036, respectively). The number of Malassezia spp. cells was significantly lower in patients with active CD compared to the control group, but in non-active CD, a significant increase was observed (p = 0.005 and p = 0.020, respectively). There were no statistically significant differences in the colonization by archaea. The obtained results indicate possible correlations with the course of the CD; however, further studies of the entire archeobiome and the mycobiome are necessary in order to receive a complete picture.
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Age and Gender: Affecting the Positive Rates of Serum PAB and ANCA in Patients with Inflammatory Bowel Disease. Gastroenterol Res Pract 2021; 2021:4963641. [PMID: 34394344 PMCID: PMC8360740 DOI: 10.1155/2021/4963641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 07/22/2021] [Indexed: 11/17/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a group of immune-mediated conditions. Immune activity is varied by age and gender. The present study is aimed at investigating the effect of age and gender on the positive rates of anti-Saccharomyces cerevisiae antibodies (ASCA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-intestinal goblet cell antibodies (GAB), and antibodies to exocrine pancreas (PAB) in IBD patients. A total of 1871 hospitalized patients with confirmed IBD were included in this study. Sera were obtained from each subject for antibody measurement by indirect immunofluorescence assay. The positive rates of ANCA IgG and IgA were higher in female patients than those in male patients (P < 0.001) while the positive rate of PAB IgG was just reversed (P < 0.001). Moreover, the median ages of patients with positive ANCA IgG and IgA were higher than patients with negative antibodies (P = 0.0019 and P = 0.0110, respectively), while the median ages of patients with positive PAB IgG and IgA were significantly lower than patients with negative PAB (P < 0.0001). The serum levels of ANCA IgG and IgA were potentiated in old female patients, while serum PAB IgG was easy to be detected in the young male patients with IBD.
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20
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The Role of Biomarkers in Surgery for Ulcerative Colitis: A Review. J Clin Med 2021; 10:jcm10153362. [PMID: 34362144 PMCID: PMC8348722 DOI: 10.3390/jcm10153362] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/25/2021] [Accepted: 07/28/2021] [Indexed: 12/19/2022] Open
Abstract
Ulcerative colitis (UC) is an inflammatory condition that generally affects the rectum and extends proximally into the colon in a continuous, distal-to-proximal pattern. Surgical resection (total proctocolectomy) is the only cure for UC and is often necessary in managing complicated or refractory disease. However, recent advances in biologically targeted therapies have resulted in improved disease control, and surgery is required in only a fraction of cases. This ever-increasing array of options for medical management has added complexity to surgical decision-making. In some circumstances, the added time required to ensure failure of medical therapy can delay colectomy in patients who will ultimately need it. Indeed, many patients with severe disease undergo trials of multiple medical therapies prior to considering surgery. In severe cases of UC, continued medical management has been associated with a delay to surgical intervention and higher rates of morbidity and mortality. Biomarkers represent a burgeoning field of research, particularly in inflammatory bowel disease and cancer. This review seeks to highlight the different possible settings for surgery in UC and the role various biomarkers might play in each.
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21
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Ito N, Takeuchi I, Kyodo R, Hirano Y, Sato T, Usami M, Shimizu H, Shimizu T, Arai K. Features and Outcomes of Children with Ulcerative Colitis who Undergo a Diagnostic Change: A Single-Center Experience. Pediatr Gastroenterol Hepatol Nutr 2021; 24:357-365. [PMID: 34316470 PMCID: PMC8279826 DOI: 10.5223/pghn.2021.24.4.357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 04/07/2021] [Accepted: 05/15/2021] [Indexed: 11/20/2022] Open
Abstract
PURPOSE A change in diagnosis from ulcerative colitis (UC) to Crohn's disease (CD) has been reported in pediatric inflammatory bowel disease; however, only a few clinical characteristics and predictors of this diagnostic change have been reported. We aimed to describe the clinical characteristics of patients with UC who underwent a change in diagnosis to CD and identify variables associated with the change. METHODS The medical records of pediatric patients with UC who were followed up at the National Center for Child Health and Development between 2006 and 2019 were retrospectively reviewed. Clinical data on disease phenotype, laboratory parameters, endoscopic findings, and treatment of patients whose diagnosis changed to CD (cCD) were compared to those of patients whose diagnosis remained UC (rUC). RESULTS Among the 111 patients initially diagnosed with UC, 11 (9.9%) patients were subsequently diagnosed with CD during follow-up. There was no significant difference between the cCD and rUC groups in terms of sex, age at initial diagnosis, and the extent and severity of disease at initial diagnosis. Albumin and hemoglobin levels were significantly lower in the cCD group than in the rUC group. The proportion of patients who required biologics was significantly higher in the cCD group than in the rUC group (p<0.05). CONCLUSION Approximately 10% children initially diagnosed with UC were subsequently diagnosed with CD. Hypoalbuminemia and anemia at initial diagnosis and use of biologics could be predictors of this diagnostic change.
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Affiliation(s)
- Natsuki Ito
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan.,Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Ichiro Takeuchi
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan
| | - Reiko Kyodo
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan.,Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yuri Hirano
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan
| | - Takuro Sato
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan
| | - Masaaki Usami
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan
| | - Hirotaka Shimizu
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Katsuhiro Arai
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan
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Venkateswaran N, Weismiller S, Clarke K. Indeterminate Colitis - Update on Treatment Options. J Inflamm Res 2021; 14:6383-6395. [PMID: 34876831 PMCID: PMC8643196 DOI: 10.2147/jir.s268262] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 11/17/2021] [Indexed: 12/30/2022] Open
Abstract
Indeterminate colitis (IC) is described in approximately 5-15% of patients with inflammatory bowel disease (IBD). It usually reflects a difficulty or lack of clarity in distinguishing between ulcerative colitis (UC) and Crohn's disease (CD) on biopsy or colectomy specimens. The diagnostic difficulty may explain the variability in the reported prevalence and incidence of IC. Clinically, most IC patients tend to evolve over time to a definite diagnosis of either UC or CD. IC has also been interchangeably described as inflammatory bowel disease unclassified (IBDU). This review offers an overview of the available limited literature on the conventional medical and surgical treatments for IC. In contrast to the numerous studies on the medical management of UC and CD, there are very few data from dedicated controlled trials on the treatment of IC. The natural evolution of IC more closely mimics UC. Regarding medical options for treatment, most patients diagnosed with IC are treated similarly to UC, and treatment choices are based on disease severity. Others are managed similarly to CD if there are features suggestive of CD, including fissures, skin tags, or rectal sparing. In medically refractory IC, surgical treatment options are limited and include total proctocolectomy (TPC) and ileal pouch-anal anastomosis (IPAA), with its associated risk factors and complications. Post-surgical complications and pouch failure rates were historically thought to be more common in IC patients, but recent meta-analyses reveal similar rates between UC and IC patients. Future therapies in IBD are focused on known mechanisms in the disease pathways of UC and CD. Owing to the lack of IC-specific studies, clinicians have traditionally and historically extrapolated the data to IC patients based on their symptomatology, clinical course, and endoscopic findings.
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Affiliation(s)
- Niranjani Venkateswaran
- Division of General Internal Medicine, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA, USA
| | - Scott Weismiller
- Division of General Internal Medicine, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA, USA
| | - Kofi Clarke
- Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA, USA
- Correspondence: Kofi Clarke Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USATel +1 717-531-8741Fax +1 717-531-6770 Email
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Longo S, Chieppa M, Cossa LG, Spinelli CC, Greco M, Maffia M, Giudetti AM. New Insights into Inflammatory Bowel Diseases from Proteomic and Lipidomic Studies. Proteomes 2020; 8:proteomes8030018. [PMID: 32784952 PMCID: PMC7565982 DOI: 10.3390/proteomes8030018] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 08/04/2020] [Accepted: 08/07/2020] [Indexed: 12/19/2022] Open
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) represent the two main forms of chronic inflammatory bowel diseases (IBD). The exact IBD etiology is not yet revealed but CD and UC are likely induced by an excessive immune response against normal constituents of the intestinal microbial flora. IBD diagnosis is based on clinical symptoms often combined with invasive and costly procedures. Thus, the need for more non-invasive markers is urgent. Several routine laboratory investigations have been explored as indicators of intestinal inflammation in IBD, including blood testing for C-reactive protein, erythrocyte sedimentation rate, and specific antibodies, in addition to stool testing for calprotectin and lactoferrin. However, none has been universally adopted, some have been well-characterized, and others hold great promise. In recent years, the technological developments within the field of mass spectrometry (MS) and bioinformatics have greatly enhanced the ability to retrieve, characterize, and analyze large amounts of data. High-throughput research allowed enhancing the understanding of the biology of IBD permitting a more accurate biomarker discovery than ever before. In this review, we summarize currently used IBD serological and stool biomarkers and how proteomics and lipidomics are contributing to the identification of IBD biomarkers.
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Affiliation(s)
- Serena Longo
- Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni 165, 73100 Lecce, Italy; (S.L.); (L.G.C.); (C.C.S.)
| | - Marcello Chieppa
- National Institute of Gastroenterology “S. de Bellis”, Institute of Research, Via Turi, 27, 70013 Castellana Grotte, Italy;
| | - Luca G. Cossa
- Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni 165, 73100 Lecce, Italy; (S.L.); (L.G.C.); (C.C.S.)
| | - Chiara C. Spinelli
- Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni 165, 73100 Lecce, Italy; (S.L.); (L.G.C.); (C.C.S.)
| | - Marco Greco
- Department of Mathematics and Physics “Ennio De Giorgi”, University of Salento, via Monteroni, 73100 Lecce, Italy;
| | - Michele Maffia
- Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni 165, 73100 Lecce, Italy; (S.L.); (L.G.C.); (C.C.S.)
- Correspondence: (M.M.); (A.M.G.)
| | - Anna M. Giudetti
- Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni 165, 73100 Lecce, Italy; (S.L.); (L.G.C.); (C.C.S.)
- Correspondence: (M.M.); (A.M.G.)
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Moiseev S, Cohen Tervaert JW, Arimura Y, Bogdanos DP, Csernok E, Damoiseaux J, Ferrante M, Flores-Suárez LF, Fritzler MJ, Invernizzi P, Jayne D, Jennette JC, Little MA, McAdoo SP, Novikov P, Pusey CD, Radice A, Salama AD, Savige JA, Segelmark M, Shoenfeld Y, Sinico RA, Sousa MJ, Specks U, Terrier B, Tzioufas AG, Vermeire S, Zhao MH, Bossuyt X. 2020 international consensus on ANCA testing beyond systemic vasculitis. Autoimmun Rev 2020; 19:102618. [PMID: 32663621 DOI: 10.1016/j.autrev.2020.102618] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 03/08/2020] [Indexed: 02/07/2023]
Abstract
This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.
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Affiliation(s)
- Sergey Moiseev
- Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia.
| | - Jan Willem Cohen Tervaert
- Department of Medicine, Division of Rheumatology, University of Alberta, Edmonton, Canada and Maastricht University, Maastricht, The Netherlands
| | - Yoshihiro Arimura
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Dimitrios P Bogdanos
- Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece
| | - Elena Csernok
- Department of Internal Medicine, Rheumatology and Immunology, Vasculitis-Center Tübingen-Kirchheim, Medius Klinik Kirchheim, University of Tübingen, Kirchheim-Teck, Germany
| | - Jan Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Marc Ferrante
- University Hospitals Leuven, Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium
| | - Luis Felipe Flores-Suárez
- Primary Systemic Vasculitides Clinic, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
| | - Marvin J Fritzler
- Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Pietro Invernizzi
- Division Gastroenterology and Center for Autoimmune Liver Diseases, University of Milano-Bicocca School of Medicine, Monza, Italy
| | - David Jayne
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - J Charles Jennette
- Division of Nephropathology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA
| | - Mark A Little
- Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Dublin, Ireland
| | - Stephen P McAdoo
- Centre for Inflammatory Disease, Department of Medicine, Imperial College London, London, UK
| | - Pavel Novikov
- Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Charles D Pusey
- Centre for Inflammatory Disease, Department of Medicine, Imperial College London, London, UK
| | - Antonella Radice
- Microbiology and Virology Institute, ASST Santi Paolo e Carlo, San Carlo Borromeo Hospital, Milan, Italy
| | - Alan D Salama
- UCL Department of Renal Medicine, Royal Free Hospital, London, UK
| | - Judith A Savige
- Department of Medicine, Melbourne Health, University of Melbourne, Melbourne, Australia
| | - Mårten Segelmark
- Department of Clinical Sciences, Lund University, Department of Nephrology and Rheumatology, Skane University Hospital, Lund, Sweden
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Renato A Sinico
- Department of Medicine and Surgery, Università degli Studi di Milano-Bicocca, Monza, Italy
| | - Maria-José Sousa
- Immunopathology and Autoimmunity Department, Centro de Medicina Laboratorial Germano de Sousa, Lisbon, Portugal
| | - Ulrich Specks
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Benjamin Terrier
- Department of Internal Medicine, National Referral Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
| | - Athanasios G Tzioufas
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Severine Vermeire
- University Hospitals Leuven, Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium
| | - Ming-Hui Zhao
- Renal Division, Peking University First Hospital, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Peking-Tsinghua Centre for Life Sciences, Beijing, China
| | - Xavier Bossuyt
- Laboratory Medicine, University Hospitals Leuven, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
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25
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Chen P, Zhou G, Lin J, Li L, Zeng Z, Chen M, Zhang S. Serum Biomarkers for Inflammatory Bowel Disease. Front Med (Lausanne) 2020; 7:123. [PMID: 32391365 PMCID: PMC7188783 DOI: 10.3389/fmed.2020.00123] [Citation(s) in RCA: 117] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 03/20/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic, inflammatory disorder of the gastrointestinal tract. As the novel therapeutic goal and biologicals are widely recognized, accurate assessment of disease and prediction of therapeutic response have become a crucial challenge in clinical practice. Also, because of the continuously rising incidence, convenient and economical methods of diagnosis and clinical assessment are urgently needed. Recently, serum biomarkers have made a great progress and become a focus in IBD study because they are non-invasive, convenient, and relatively inexpensive than are markers in biopsy tissue, stool, breath, and other body fluids. Aims: To review the available data on serological biomarkers for IBD. Methods: We searched PubMed using predefined key words on relevant literatures of serum biomarkers regarding diagnosis, evaluation of therapeutic efficacy, surveillance of disease activity, and assessment of prognosis for IBD. Results: We reviewed serological biomarkers that are well-established and widely used (e.g., C-reactive protein), newly discovered biomarkers (e.g., cytokines, antibodies, and non-coding RNAs), and also recently advancements in serological biomarkers (e.g., metabolomics and proteomics) that are used in different aspects of IBD management. Conclusions: With such a wealth of researches, to date, there are still no ideal serum biomarkers for IBD. Serum profiling and non-coding RNAs are just starting to blossom but reveal great promise for future clinical practice. Combining different biomarkers can be valuable in improving performance of disease evaluation.
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Affiliation(s)
- Peng Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Gaoshi Zhou
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jingxia Lin
- Division of Blood Transfusion, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Li Li
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhirong Zeng
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shenghong Zhang
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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26
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Goren I, Godny L, Reshef L, Yanai H, Gophna U, Tulchinsky H, Dotan I. Starch Consumption May Modify Antiglycan Antibodies and Fecal Fungal Composition in Patients With Ileo-Anal Pouch. Inflamm Bowel Dis 2019; 25:742-749. [PMID: 30535148 DOI: 10.1093/ibd/izy370] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Inflammatory bowel diseases (IBDs) are characterized by serologic responses to glycans. Patients with ulcerative colitis (UC) after proctocolectomy with ileo-anal anastomosis (pouch surgery) may develop inflammation (pouchitis) that resembles Crohn's disease (CD). We hypothesized that patients' serologic responses were affected by their consumption of dietary sugars. This study analyzed the correlations between antiglycan antibody expression and dietary sugar consumption in patients with UC pouch and the evolution in antibody levels over time. METHODS Patients were followed prospectively for 2 consecutive visits. The following antiglycan carbohydrate antibodies were detected by enzyme-linked immunosorbent assay: antichitobioside (ACCA), antilaminaribioside (ALCA), antimannobioside (AMCA), and anti-Saccharomyces cerevisiae (ASCA) antibodies. Patients completed a food frequency questionnaire. The fungal community in patients' fecal samples was analyzed by sequencing the internal transcribed spacer 2 (ITS2) region of nuclear ribosomal DNA. RESULTS We included 75 UC pouch patients aged 45.2 ± 14 years who underwent pouch surgery 9.8 ± 6.7 years previously. Of these patients, 34.7% (n = 26) showed seropositivity for antiglycan antibodies. Starch consumption was significantly higher in patients with positive serologic responses (P = 0.05). Higher starch consumption was associated with higher AMCA and ACCA titers, which increased by 4.08% (0.8%-7.4%; P = 0.014) and 4.8% (0.7%-9.1%; P = 0.007), respectively, for each 10-g increase of dietary starch. The per-patient change in the relative abundance of Candida albicans in fecal samples correlated positively with changes in starch consumption (Spearman's r = 0.72; P = 0.012). CONCLUSIONS Starch consumption correlated with positive antiglycan serology (ACCA and AMCA), suggesting that increased dietary starch intake may promote a specific immune response in patients with IBD.
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Affiliation(s)
- Idan Goren
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Lihi Godny
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Leah Reshef
- Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Henit Yanai
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Uri Gophna
- Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Hagit Tulchinsky
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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27
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Limon JJ, Tang J, Li D, Wolf AJ, Michelsen KS, Funari V, Gargus M, Nguyen C, Sharma P, Maymi VI, Iliev ID, Skalski JH, Brown J, Landers C, Borneman J, Braun J, Targan SR, McGovern DPB, Underhill DM. Malassezia Is Associated with Crohn's Disease and Exacerbates Colitis in Mouse Models. Cell Host Microbe 2019; 25:377-388.e6. [PMID: 30850233 DOI: 10.1016/j.chom.2019.01.007] [Citation(s) in RCA: 301] [Impact Index Per Article: 50.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 12/19/2018] [Accepted: 01/15/2019] [Indexed: 01/09/2023]
Abstract
Inflammatory bowel disease (IBD) is characterized by alterations in the intestinal microbiota and altered immune responses to gut microbiota. Evidence is accumulating that IBD is influenced by not only commensal bacteria but also commensal fungi. We characterized fungi directly associated with the intestinal mucosa in healthy people and Crohn's disease patients and identified fungi specifically abundant in patients. One of these, the common skin resident fungus Malassezia restricta, is also linked to the presence of an IBD-associated polymorphism in the gene for CARD9, a signaling adaptor important for anti-fungal defense. M. restricta elicits innate inflammatory responses largely through CARD9 and is recognized by Crohn's disease patient anti-fungal antibodies. This yeast elicits strong inflammatory cytokine production from innate cells harboring the IBD-linked polymorphism in CARD9 and exacerbates colitis via CARD9 in mouse models of disease. Collectively, these results suggest that targeting specific commensal fungi may be a therapeutic strategy for IBD.
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Affiliation(s)
- Jose J Limon
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Jie Tang
- Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Dalin Li
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Andrea J Wolf
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Kathrin S Michelsen
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Vince Funari
- Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Matthew Gargus
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Christopher Nguyen
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Purnima Sharma
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Viviana I Maymi
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Iliyan D Iliev
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Joseph H Skalski
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, USA
| | - Jordan Brown
- Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Carol Landers
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - James Borneman
- Department of Plant Pathology and Microbiology, University of California, Riverside, Riverside, CA 92521, USA
| | - Jonathan Braun
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Stephan R Targan
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Dermot P B McGovern
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - David M Underhill
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
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28
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Zhang L, Wu TT. Inflammatory Bowel Disease. SURGICAL PATHOLOGY OF NON-NEOPLASTIC GASTROINTESTINAL DISEASES 2019:373-424. [DOI: 10.1007/978-3-030-15573-5_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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29
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Abstract
PURPOSE OF REVIEW The intestinal microbiota plays a central role in inflammatory diseases of the gut. Although most investigations regarding how the mucosal immune system interacts with the microbiota have focused on bacteria, recent studies are elucidating the additional role of commensal fungi in health and disease in the gut. RECENT FINDINGS New technical approaches are defining the makeup of the fungal communities in the intestines of humans and mice. The reported composition of these communities is influenced by the approaches used to define the fungi. Changes in the intestinal mycobiota are associated with gut inflammation in patients with inflammatory bowel disease and in mouse models of colitis. Recent studies are beginning to elucidate the mechanisms by which the mucosal immune system interacts with and is influenced by intestinal fungi. SUMMARY Studies clearly demonstrate the presence of intestinal fungi and document the ability of the mucosal immune system to recognize and respond to fungi. Future studies will further investigate whether intestinal fungi directly influence intestinal disease and what cellular, molecular, and genetic mechanisms contribute.
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30
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Chandradevan R, Hofmekler T, Mondal K, Harun N, Venkateswaran S, Somineni HK, Ballengee CR, Kim MO, Griffiths A, Noe JD, Crandall WV, Snapper S, Rabizadeh S, Rosh JR, Walters TD, Bertha M, Dubinsky MC, Denson LA, Sauer CG, Markowitz JF, LeLeiko NS, Hyams JS, Kugathasan S. Evolution of Pediatric Inflammatory Bowel Disease Unclassified (IBD-U): Incorporated With Serological and Gene Expression Profiles. Inflamm Bowel Dis 2018; 24:2285-2290. [PMID: 29860529 DOI: 10.1093/ibd/izy136] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) mainly consists of Crohn's disease (CD) and ulcerative colitis (UC). About 10%-15% of patients with IBD cannot be firmly diagnosed with CD or UC; hence, they are initially diagnosed as inflammatory bowel disease unclassified (IBD-U). Having a firm diagnosis is clearly preferred to guide treatment choices, and better understanding of the nature of IBD-U is required. METHODS We performed an analysis of a subset of pediatric subjects from an inception IBD cohort of patients initially enrolled in a prospective multicenter study (the RISK study). Initial diagnosis and 2-year follow-up data from the subjects diagnosed with IBD-U were analyzed. An expert panel verified final diagnosis using predefined criteria as a guide. Serological and disease-relevant ileal and rectal tissue gene expression profiles were investigated. The use and the time to initiate anti-TNFα treatment was analyzed among the outcome groups. RESULTS A total of 1411 subjects were enrolled with initial diagnosis of IBD, and among them, 136 subjects were initially diagnosed as IBD-U at enrollment. And 26% were reclassified as UC and 14% as CD within 2 years of diagnosis, while 60% remained as IBD-U. Of those who were reclassified, there was a 2:1 ratio, UC (n = 35) to CD (n = 19). The molecular and serological features of IBD-U at the end of follow-up were very similar to UC and very different from CD. There was less likelihood of receiving anti-TNFα agents if the diagnosis was IBD-U compared with CD (P < 0.0001). CONCLUSIONS In our cohort, 60% of the IBD-U subjects remained as unclassified at 2 years; of those subsequently classified, a higher percentage followed a course more similar to UC. Most of the IBD-U subjects at diagnosis had serological and molecular signatures that are very similar to UC. Although the atypical presentations made the clinician to make an interim diagnosis of IBD-U, results of the molecular and serological factors performed at the time of diagnosis suggests that they were very similar to UC. However, long-term studies are needed to better understand the natural history and molecular characterization of pediatric onset IBD-U. 10.1093/ibd/izy136_video1Video 1.Video 1. Watch now at https://academic.oup.com/ibd/article-lookup/doi/10.1093/ibd/izy136izy136.video15791389938001.
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Affiliation(s)
- Raguraj Chandradevan
- Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Tatyana Hofmekler
- Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, Georgia, USA.,Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Kajari Mondal
- Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Nusrat Harun
- Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA
| | - Suresh Venkateswaran
- Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Hari K Somineni
- Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Cortney R Ballengee
- Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, Georgia, USA.,Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Mi-Ok Kim
- Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA
| | - Anne Griffiths
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Joshua D Noe
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Wallace V Crandall
- Department of Pediatric Gastroenterology, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Scott Snapper
- Department of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Shervin Rabizadeh
- Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Joel R Rosh
- Department of Pediatrics, Goryeb Children's Hospital, Morristown, New Jersey, USA
| | - Thomas D Walters
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Madeline Bertha
- Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Marla C Dubinsky
- Department of Pediatrics, Mount Sinai Hospital, New York, New York, USA
| | - Lee A Denson
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Cary G Sauer
- Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, Georgia, USA.,Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | | | - Neal S LeLeiko
- Division of Pediatric Gastroenterology, Nutrition and Liver Disease, Hasbro Children Hospital, Brown Medical School, Providence, Rhode Island, USA
| | - Jeffrey S Hyams
- Division of Digestive Diseases, Hepatology, and Nutrition Connecticut Children's Medical Center, Hartford, Connecticut, USA
| | - Subra Kugathasan
- Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, Georgia, USA.,Children's Healthcare of Atlanta, Atlanta, Georgia, USA
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31
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Jiang KF, Fan YH. Serological markers and inflammatory bowel disease: Prevalence of serum markers and their diagnostic value in inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2018; 26:1487-1493. [DOI: 10.11569/wcjd.v26.i25.1487] [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] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic nonspecific disease of the digestive tract that is caused by genetic and environmental factors, including ulcerative colitis, Crohn's disease, and unclassified IBD. At present, the diagnosis of IBD depends mainly on clinical manifestations, imaging changes, colonoscopy, and pathological biopsy, but there exist some limitations. The advantages of serological markers in IBD diagnosis are prominent, and a large number of relevant studies have been reported. This paper reviews the diagnostic and therapeutic value of serological markers in IBD, with an aim to clarify their role in the diagnosis and treatment of IBD.
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Affiliation(s)
- Ke-Fang Jiang
- Department of Gastroenterology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
| | - Yi-Hong Fan
- Department of Gastroenterology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
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32
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Abstract
Fungi are increasingly being recognized as common members of the microbiomes found on nearly all mucosal surfaces, and interest is growing in understanding how these organisms may contribute to health and disease. In this review, we investigate recent developments in our understanding of the fungal microbiota or "mycobiota" including challenges faced in characterizing it, where these organisms are found, their diversity, and how they interact with host immunity. Growing evidence indicates that, like the bacterial microbiota, the fungal microbiota is often altered in disease states, and increasingly studies are being designed to probe the functional consequences of such fungal dysbiosis on health and disease.
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Affiliation(s)
- Jose J Limon
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA
| | - Joseph H Skalski
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, USA
| | - David M Underhill
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
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33
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Huseyin CE, O'Toole PW, Cotter PD, Scanlan PD. Forgotten fungi-the gut mycobiome in human health and disease. FEMS Microbiol Rev 2017; 41:479-511. [PMID: 28430946 DOI: 10.1093/femsre/fuw047] [Citation(s) in RCA: 170] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Accepted: 01/04/2017] [Indexed: 12/11/2022] Open
Abstract
The human body is home to a complex and diverse microbial ecosystem that plays a central role in host health. This includes a diversity of fungal species that is collectively referred to as our 'mycobiome'. Although research into the mycobiome is still in its infancy, its potential role in human disease is increasingly recognised. Here we review the existing literature available on the human mycobiota with an emphasis on the gut mycobiome, including how fungi interact with the human host and other microbes. In doing so, we provide a comprehensive critique of the methodologies available to research the human mycobiota as well as highlighting the latest research findings from mycological surveys of different groups of interest including infants, obese and inflammatory bowel disease cohorts. This in turn provides new insights and directions for future studies in this burgeoning research area.
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Affiliation(s)
- Chloe E Huseyin
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork P61 C996, Ireland.,APC Microbiome Institute, Biosciences Institute, University College Cork, Cork T12 YT20 Ireland.,School of Microbiology, University College Cork, Cork T12 YT20, Ireland
| | - Paul W O'Toole
- APC Microbiome Institute, Biosciences Institute, University College Cork, Cork T12 YT20 Ireland.,School of Microbiology, University College Cork, Cork T12 YT20, Ireland
| | - Paul D Cotter
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork P61 C996, Ireland.,APC Microbiome Institute, Biosciences Institute, University College Cork, Cork T12 YT20 Ireland
| | - Pauline D Scanlan
- APC Microbiome Institute, Biosciences Institute, University College Cork, Cork T12 YT20 Ireland
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Ashton JJ, Ennis S, Beattie RM. Early-onset paediatric inflammatory bowel disease. THE LANCET CHILD & ADOLESCENT HEALTH 2017; 1:147-158. [PMID: 30169204 DOI: 10.1016/s2352-4642(17)30017-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Revised: 06/08/2017] [Accepted: 06/14/2017] [Indexed: 12/27/2022]
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Smids C, Horjus Talabur Horje CS, Groenen MJM, van Koolwijk EHM, Wahab PJ, van Lochem EG. The value of serum antibodies in differentiating inflammatory bowel disease, predicting disease activity and disease course in the newly diagnosed patient. Scand J Gastroenterol 2017; 52:1104-1112. [PMID: 28661185 DOI: 10.1080/00365521.2017.1344875] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Data on serum antibodies in untreated adult inflammatory bowel disease (IBD) patients at diagnosis are scarcely available, and results on the stability of antibody presence over time are inconsistent. Our aim was to investigate antibodies in newly diagnosed, untreated IBD patients in relation to disease phenotype and course. Furthermore, we analyzed antibody presence over time. METHODS Baseline anti-Saccharomyces cerevisiae antibodies (ASCA), anti-chitobioside carbohydrate antibodies (ACCA), anti-laminaribioside carbohydrate antibodies (ALCA) and anti-mannobioside carbohydrate antibodies (AMCA) were measured with enzyme-linked immunosorbent assays and perinuclear anti-neutrophilic cytoplasmic antibodies (pANCA) was measured by indirect immunofluorescence in serum of 120 untreated IBD patients at diagnosis and 19 healthy controls. Antibodies were related to disease outcomes. Serial measurements were available in 71 patients. RESULTS The combination of pANCA and ASCA enabled good discrimination between UC and CD (p = .004). Antibody presence was relatively stable over time, even though there were significant changes in concentrations. There was a trend towards larger fluctuations in concentration with immunosuppressive medication. Baseline pANCA in UC patients correlated with calprotectin values (rho = .545, p = .019) and change in pANCA status over time was associated with disease activity at that moment. No associations were found with antibodies at diagnosis and disease outcomes. CONCLUSION Antibody profiles at diagnosis support the distinction between CD and UC. Anti-glycan antibodies are reasonably stable over time, but may fluctuate under the influence of immunosuppressive treatment which may explain the inconsistency in findings hitherto. The appearance or disappearance of pANCA antibodies during follow-up correlated with disease activity in UC and may be used in disease monitoring.
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Affiliation(s)
- Carolijn Smids
- a Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology , Rijnstate Hospital , Arnhem , The Netherlands
| | - Carmen S Horjus Talabur Horje
- a Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology , Rijnstate Hospital , Arnhem , The Netherlands
| | - Marcel J M Groenen
- a Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology , Rijnstate Hospital , Arnhem , The Netherlands
| | - Elly H M van Koolwijk
- b Department of Microbiology and Immunology , Rijnstate Hospital , Arnhem , The Netherlands
| | - Peter J Wahab
- a Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology , Rijnstate Hospital , Arnhem , The Netherlands
| | - Ellen G van Lochem
- b Department of Microbiology and Immunology , Rijnstate Hospital , Arnhem , The Netherlands
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Birimberg-Schwartz L, Zucker DM, Akriv A, Cucchiara S, Cameron FL, Wilson DC, Lazowska I, Yianni L, Paul SP, Romano C, Kolacek S, Buderus S, Pærregaard A, Russell RK, Escher JC, Turner D. Development and Validation of Diagnostic Criteria for IBD Subtypes Including IBD-unclassified in Children: a Multicentre Study From the Pediatric IBD Porto Group of ESPGHAN. J Crohns Colitis 2017; 11:1078-1084. [PMID: 28430891 DOI: 10.1093/ecco-jcc/jjx053] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 04/11/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND The revised Porto criteria identify subtypes of paediatric inflammatory bowel diseases: ulcerative colitis [UC], atypical UC, inflammatory bowel disease unclassified [IBDU], and Crohn's disease [CD]. Others have proposed another subclassifiction of Crohn's colitis. In continuation of the Porto criteria, we aimed to derive and validate criteria, termed "PIBD-classes," for standardising the classification of the different IBD subtypes. METHODS This was a multicentre retrospective longitudinal study from 23 centres affiliated with the Port -group of ESPGHAN. Both a hypothesis-driven judgmental approach and mathematical classification and regression tree [CART] modelling were used for creating a diagnostic algorithm. Since small bowel inflammation is easily recognised as CD, we focused here primarily on the phenotype of colitis. RESULTS In all, 749 IBD children were enrolled: 236 [32%] Crohn's colitis, 272 [36%] UC and 241 [32%] IBDU [age 10.9 ± 3.6 years] with a median follow-up of 2.8 years (interquartile range [IQR] 1.7-4.3). A total of 23 features were clustered in three classes according to their prevalence in UC: six class-1 features [0% prevalence in UC], 12 class-2 features [< 5% prevalence], and five class-3 features [5-10% prevalence]. According to the algorithm, the disease should be classified as UC if no features exist in any of the classes. When at least one feature exists, different combinations classify the disease into atypical UC, IBDU or CD. The algorithm differentiated UC from CD and IBDU with 80% sensitivity (95% confidence interval [CI] 71-88%) and 84% specificity [77-89%], and CD from IBDU and UC with 78% sensitivity [67-87%] and 94% specificity [89-97%]. CONCLUSIONS The validated PIBD-classes algorithm can adequately classify children with IBD into small bowel CD, colonic CD, IBDU, atypical UC, and UC.
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Affiliation(s)
| | - David M Zucker
- Department of Statistics, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Amichay Akriv
- Department of Statistics, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Salvatore Cucchiara
- Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - Fiona L Cameron
- Child Life and Health, University of Edinburgh and Royal Hospital for Children, Edinburgh, UK
| | - David C Wilson
- Child Life and Health, University of Edinburgh and Royal Hospital for Children, Edinburgh, UK
| | - Iza Lazowska
- Paediatric Gastroenterology Unit, Medical University of Warsaw, Warsaw, Poland
| | - Lambri Yianni
- University Hospital Southampton NHS Foundation Trust, Child Health, Southampton,UK
| | - Siba Prosad Paul
- Paediatric Gastroenterology, Bristol Royal Hospital for Children,Bristol, UK
| | - Claudio Romano
- Pediatric Gastroenterology and Endoscopy, University of Messina, Messina, Italy
| | - Sanja Kolacek
- Paediatric Gastroenterology Unit, Children's Hospital Zagreb, University Medical School, Zagreb, Croatia
| | - Stephan Buderus
- St.-Marien-Hospital, Department of Pediatrics, Bonn, Germany
| | - Anders Pærregaard
- Department of Paediatrics, Hvidovre University Hospital, Copenhagen, Denmark
| | - Richard K Russell
- Paediatric Gastroenterology Unit, Royal Hospital for Children, Glasgow, UK
| | - Johanna C Escher
- Pediatric Gastroenterology, Erasmus MC-Sophia, Rotterdam, The Netherlands
| | - Dan Turner
- Institute of Pediatric Gastroenterology, Shaare Zedek Medical Centre, Jerusalem, Israel
- Department of Statistics, Hebrew University of Jerusalem, Jerusalem, Israel
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Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, Burisch J, Gecse KB, Hart AL, Hindryckx P, Langner C, Limdi JK, Pellino G, Zagórowicz E, Raine T, Harbord M, Rieder F. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis 2017; 11:649-670. [PMID: 28158501 DOI: 10.1093/ecco-jcc/jjx008] [Citation(s) in RCA: 1266] [Impact Index Per Article: 158.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 02/01/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Fernando Magro
- Department of Pharmacology and Therapeutics, University of Porto; MedInUP, Centre for Drug Discovery and Innovative Medicines; Centro Hospitalar São João, Porto, Portugal
| | | | - Rami Eliakim
- Department of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Sandro Ardizzone
- Gastrointestinal Unit ASST Fatebenefratelli Sacco-University of Milan-Milan, Italy
| | - Alessandro Armuzzi
- IBD Unit Complesso Integrato Columbus, Gastroenterological and Endocrino-Metabolical Sciences Department, Fondazione Policlinico Universitario Gemelli Universita' Cattolica del Sacro Cuore, Rome, Italy
| | - Manuel Barreiro-de Acosta
- Department of Gastroenterology, IBD Unit, University Hospital Santiago De Compostela (CHUS), A Coruña, Spain
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Krisztina B Gecse
- First Department of Medicine, Semmelweis University, Budapest,Hungary
| | | | - Pieter Hindryckx
- Department of Gastroenterology, University Hospital of Ghent, Ghent, Belgium
| | - Cord Langner
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust; Institute of Inflammation and Repair, University of Manchester, Manchester, UK
| | - Gianluca Pellino
- Unit of General Surgery, Second University of Naples,Napoli, Italy
| | - Edyta Zagórowicz
- Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Oncological Gastroenterology Warsaw; Medical Centre for Postgraduate Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Warsaw, Poland
| | - Tim Raine
- Department of Medicine, University of Cambridge, Cambridge,UK
| | - Marcus Harbord
- Imperial College London; Chelsea and Westminster Hospital, London,UK
| | - Florian Rieder
- Department of Pathobiology /NC22, Lerner Research Institute; Department of Gastroenterology, Hepatology and Nutrition/A3, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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Rinawi F, Assa A, Eliakim R, Mozer-Glassberg Y, Nachmias Friedler V, Niv Y, Rosenbach Y, Silbermintz A, Zevit N, Shamir R. The natural history of pediatric-onset IBD-unclassified and prediction of Crohn's disease reclassification: a 27-year study. Scand J Gastroenterol 2017; 52:558-563. [PMID: 28128677 DOI: 10.1080/00365521.2017.1282008] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) in patients who were initially diagnosed as inflammatory bowel disease-unclassified (IBDU) remains challenging. Our aims were to describe the natural history of pediatric-onset IBDU patients during prolonged period of follow up and to identify associated predictors for CD reclassification among them. MATERIALS AND METHODS In this retrospective single center study, out of 723 patients with pediatric onset IBD, we identified 53 patients (7.3%) diagnosed with IBDU at the Schneider Children's Medical Center of Israel between 1986 and 2013. Potential predictors for CD reclassification including age at diagnosis, gender, clinical manifestations, disease extent and laboratory findings were assessed. RESULTS The median follow-up was 6.8 (± 6.7) years. Reclassification to CD was observed in 24/53 (45%) of patients. The median interval from diagnosis to CD reclassification was 9.4 years. In 58% of these patients, CD reclassification occurred within 5 years from diagnosis. Multivariate Cox models showed that familial history of CD and hypoalbuminemia at diagnosis were significantly associated with CD reclassification (HR 11.3, p = .02 and HR 5.3, p = .03, respectively). All other assessed clinical, laboratory and endoscopic parameters did not serve as predictors for CD reclassification later on. CONCLUSIONS In our cohort, a substantial high proportion of pediatric onset IBDU patients were later re-diagnosed as CD. Only a family history of CD and hypoalbuminemia could predict reclassification among IBDU patients.
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Affiliation(s)
- Firas Rinawi
- a Institute of Gastroenterology, Nutrition and Liver Diseases , Schneider Children's Medical Center of Israel , Petach Tikva , Israel
| | - Amit Assa
- a Institute of Gastroenterology, Nutrition and Liver Diseases , Schneider Children's Medical Center of Israel , Petach Tikva , Israel.,b Sackler Faculty of Medicine , Tel-Aviv University , Tel Aviv , Israel
| | - Rami Eliakim
- b Sackler Faculty of Medicine , Tel-Aviv University , Tel Aviv , Israel.,c Department of Gastroenterology , Sheba Medical Center -Tel Hashomer , Tel Aviv , Israel
| | - Yael Mozer-Glassberg
- a Institute of Gastroenterology, Nutrition and Liver Diseases , Schneider Children's Medical Center of Israel , Petach Tikva , Israel.,b Sackler Faculty of Medicine , Tel-Aviv University , Tel Aviv , Israel
| | - Vered Nachmias Friedler
- a Institute of Gastroenterology, Nutrition and Liver Diseases , Schneider Children's Medical Center of Israel , Petach Tikva , Israel
| | - Yaron Niv
- b Sackler Faculty of Medicine , Tel-Aviv University , Tel Aviv , Israel.,d Department of Gastroenterology , Rabin Medical Center , Petach Tikva , Israel
| | - Yoram Rosenbach
- a Institute of Gastroenterology, Nutrition and Liver Diseases , Schneider Children's Medical Center of Israel , Petach Tikva , Israel
| | - Ari Silbermintz
- a Institute of Gastroenterology, Nutrition and Liver Diseases , Schneider Children's Medical Center of Israel , Petach Tikva , Israel
| | - Noam Zevit
- a Institute of Gastroenterology, Nutrition and Liver Diseases , Schneider Children's Medical Center of Israel , Petach Tikva , Israel.,b Sackler Faculty of Medicine , Tel-Aviv University , Tel Aviv , Israel
| | - Raanan Shamir
- a Institute of Gastroenterology, Nutrition and Liver Diseases , Schneider Children's Medical Center of Israel , Petach Tikva , Israel.,b Sackler Faculty of Medicine , Tel-Aviv University , Tel Aviv , Israel
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D'Arcangelo G, Aloi M. Inflammatory Bowel Disease-Unclassified in Children: Diagnosis and Pharmacological Management. Paediatr Drugs 2017; 19:113-120. [PMID: 28150131 DOI: 10.1007/s40272-017-0213-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Inflammatory bowel diseases are chronic disorders of the gastrointestinal tract that include Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease-unclassified (IBDU). The latter defines a subgroup of patients with clinical and endoscopic evidence of chronic colitis, without specific features of either CD or UC. These patients will possibly be re-classified as having UC or CD during the follow-up, although a significant percentage of them will keep the diagnosis of IBDU. IBDU is the rarest subtype of IBD, both in children and in adults, although it is twice as common among the pediatric population, especially in the younger ages. The diagnosis can only be made after a comprehensive diagnostic work-up, combining clinical history, physical and laboratory examination, upper and lower gastrointestinal endoscopy, with histology and imaging of the small bowel. The therapeutic strategy is borrowed from that of UC and CD, although recent data suggest that IBDU has a lower therapeutic burden with a generally mild disease course and a good response to mesalamine. Since there are only few published data on pediatric IBDU, and no guidelines on its management are available, this review aims at summarizing the most recent evidence for the diagnostic work-up with a specific focus on medical and surgical options in the treatment of IBDU.
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Affiliation(s)
- Giulia D'Arcangelo
- Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - Marina Aloi
- Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
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40
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Wang ZZ, Shi K, Peng J. Serologic testing of a panel of five antibodies in inflammatory bowel diseases: Diagnostic value and correlation with disease phenotype. Biomed Rep 2017; 6:401-410. [PMID: 28413638 PMCID: PMC5374894 DOI: 10.3892/br.2017.860] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 01/05/2017] [Indexed: 01/01/2023] Open
Abstract
The aim of the present study was to evaluate the diagnostic value of five serological antibodies, perinuclear antineutrophil cytoplasmic antibody (pANCA), anti-Saccharomyces cerevisiae antibodies [ASCA; ASCA-immunoglobulin (IgG)and ASCA-IgA], Escherichia coli outer membrane porin C antibody (anti-OmpC) and CBir1 flagellin antibody for detection in inflammatory bowel diseases. Whether the antibody status correlated with the disease phenotype was also evaluated. Sera from 71 patients with Crohn's disease (CD), 41 patients with ulcerative colitis (UC), 78 patients with other gastrointestinal diseases and 31 healthy control subjects were investigated. Clinical data were gathered at the time of serum sampling and enzyme-linked immunosorbent assay was used to determine titers of the above mentioned five antibodies. The pANCA test exhibited a sensitivity of 53.7% for UC and the ASCA test had a sensitivity of 66.2% for CD. The prevalence of anti-OmpC was significantly higher in CD than in intestinal tuberculosis (TB), indicating that anti-OmpC may be a serologic marker distinguishing CD from TB. The pANCA+/ASCA- exhibited the best specificity for differentiating between CD and UC. In UC, the presence of pANCA was greater in the patients with moderate to severe activity than in those with mild activity. ASCA was more positive in ileal CD. Furthermore, positive ASCA-IgG or anti-OmpC implied that complicated CD and pANCA was associated with colonic CD. Seropositivity of anti-CBir1 was lowest in colonic CD.
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Affiliation(s)
- Zhi-Zhi Wang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Ke Shi
- Laboratory of the Department of Gerontology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Jie Peng
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
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41
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Vetter M, Neurath MF, Atreya R. [Crohn's disease - use of biomarkers in general practice]. MMW Fortschr Med 2017; 159:63-68. [PMID: 28224516 DOI: 10.1007/s15006-017-9279-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Affiliation(s)
- Marcel Vetter
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | | | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Ulmenweg 18, D-91054, Erlangen, Deutschland.
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Subramanian S, Ekbom A, Rhodes JM. Recent advances in clinical practice: a systematic review of isolated colonic Crohn's disease: the third IBD? Gut 2017; 66:362-381. [PMID: 27802156 DOI: 10.1136/gutjnl-2016-312673] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 09/05/2016] [Accepted: 09/06/2016] [Indexed: 12/13/2022]
Abstract
The genetics of isolated colonic Crohn's disease place it approximately midway between Crohn's disease with small intestinal involvement and UC, making a case for considering it as a separate condition. We have therefore systematically reviewed its epidemiology, pathophysiology and treatment. Key findings include a higher incidence in females (65%) and older average age at presentation than Crohn's disease at other sites, a mucosa-associated microbiota between that found in ileal Crohn's disease and UC, no response to mesalazine, but possibly better response to antitumour necrosis factor than Crohn's disease at other sites. Diagnostic distinction from UC is often difficult and also needs to exclude other conditions including ischaemic colitis, segmental colitis associated with diverticular disease and tuberculosis. Future studies, particularly clinical trials, but also historical cohorts, should assess isolated colonic Crohn's disease separately.
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Affiliation(s)
- Sreedhar Subramanian
- Institute of Translational Medicine, University of Liverpool, The Henry Wellcome Laboratory, Liverpool, UK
| | - Anders Ekbom
- Department of Medicine, Karolinska Institute, Stockholm, Sweden
| | - Jonathan M Rhodes
- Institute of Translational Medicine, University of Liverpool, The Henry Wellcome Laboratory, Liverpool, UK
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Kochhar G, Lashner B. Utility of Biomarkers in the Management of Inflammatory Bowel Disease. ACTA ACUST UNITED AC 2017; 15:105-115. [PMID: 28138859 DOI: 10.1007/s11938-017-0129-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OPINION STATEMENT Inflammatory bowel disease (IBD) is comprised of complex clinical and pathological conditions. It runs a chronic course, and proper management requires constant monitoring of disease activity. Recent evidence suggests that subjective patient scores have a poor correlation with disease activity. Endoscopy remains the gold standard for diagnosing and monitoring disease activity. As healthcare is moving towards less costly and less invasive treatments, the need for biomarkers in the management of IBD is evident. Over the last decade, several biomarkers have been found, which may correct the discrepancy between subjective patient scores and the need for endoscopy.
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Affiliation(s)
- Gursimran Kochhar
- Center for Inflammatory Bowel Diseases, Digestive Disease Institute-A31, The Cleveland Clinic Foundation, 9500, Euclid Ave Cleveland, Cleveland, OH, 44195, USA
| | - Bret Lashner
- Center for Inflammatory Bowel Diseases, Digestive Disease Institute-A31, The Cleveland Clinic Foundation, 9500, Euclid Ave Cleveland, Cleveland, OH, 44195, USA.
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Wheeler ML, Limon JJ, Underhill DM. Immunity to Commensal Fungi: Detente and Disease. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2016; 12:359-385. [PMID: 28068483 DOI: 10.1146/annurev-pathol-052016-100342] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Fungi are ubiquitous in our environment, and a healthy immune system is essential to maintain adequate protection from fungal infections. When this protection breaks down, superficial and invasive fungal infections cause diseases that range from irritating to life-threatening. Millions of people worldwide develop invasive infections during their lives, and mortality for these infections often exceeds 50%. Nevertheless, we are normally colonized with many of the same disease-causing fungi (e.g., on the skin or in the gut). Recent research is dramatically expanding our understanding of the mechanisms by which our immune systems interact with these organisms in health and disease. In this review, we discuss what is currently known about where and how the immune system interacts with common fungi.
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Affiliation(s)
- Matthew L Wheeler
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048; , ,
| | - Jose J Limon
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048; , ,
| | - David M Underhill
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048; , , .,Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, 7491 Trondheim, Norway
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45
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The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA). Autoimmun Rev 2016; 15:978-82. [DOI: 10.1016/j.autrev.2016.07.016] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 07/08/2016] [Indexed: 12/21/2022]
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Li J, Ueno A, Fort Gasia M, Luider J, Wang T, Hirota C, Jijon HB, Deane M, Tom M, Chan R, Barkema HW, Beck PL, Kaplan GG, Panaccione R, Qian J, Iacucci M, Gui X, Ghosh S. Profiles of Lamina Propria T Helper Cell Subsets Discriminate Between Ulcerative Colitis and Crohn's Disease. Inflamm Bowel Dis 2016; 22:1779-1792. [PMID: 27243594 DOI: 10.1097/mib.0000000000000811] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Distinction between 2 forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), can be challenging. Aberrant mucosal immunity suggests that CD is a T helper type 1 cell (Th1)-driven disease, whereas UC as Th2-driven response. However, whether this paradigm truly distinguishes CD from UC is controversial. We aimed to clarify the discriminating potential of lamina propria Th subsets in patients with IBD. METHODS Biopsies from 79 patients with IBD and 20 healthy controls were collected for Th subsets analysis (Th1:interferon γ [IFN-γ], T-bet; Th2:interleukin 13 [IL-13], Gata3; Th17:IL-17, RORγt; Treg:FoxP3). The receiver-operating characteristic curves were constructed to assess the discriminating ability by calculating the area under the receiver-operating characteristic curve. The equation with the highest area under the receiver-operating characteristic curve was applied to newly diagnosed patients to evaluate discriminating ability. RESULTS Patients with CD showed increased IFN-γ or T-bet cells and decreased IL-13 or Gata3 cells compared with UC. A discriminant equation composed of 4 markers (IFN-γ, T-bet, IL-13, and Gata3) yielded the highest area under the receiver-operating characteristic curve. In 36 established CD or UC, the sensitivity, specificity, positive and negative predictive probabilities were 92.6%, 55.6%, 86.2%, and 71.4% and in 14 newly diagnosed patients were 100.0%, 42.9%, 63.6%, and 100.0%. Furthermore, Gata3 cells were increased in tumor necrosis factor inhibitor therapy nonresponders compared with responders in CD. IFN-γ cells were directly and inversely proportional to disease activity in patients with CD and UC, respectively. CONCLUSIONS The Th1/Th2 paradigm can distinguish CD from UC and may be further associated with response to tumor necrosis factor inhibitor in CD and disease activity in patients with IBD.
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Affiliation(s)
- Ji Li
- *Department of Medicine/Gastroenterology, University of Calgary, Calgary, Alberta, Canada;†Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China;‡Calgary Laboratory Services, Calgary, Alberta, Canada;§Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada; and‖Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
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Abstract
There is currently no single test available to confidently diagnose cases of inflammatory bowel disease (IBD). Physicians rely on a number of diagnostic tools, including clinical evaluation, serum testing, and imaging, which are used on conjunction with endoscopic evaluation. It is often difficult to determine whether patients with abdominal pain and change in bowel habit have functional bowel symptoms or whether they have a true diagnosis of IBD. Even once a diagnosis of IBD has been made, a significant proportion of patients are labeled with the term "indeterminate colitis" where histological sampling cannot confidently subclassify patients as either Crohn's or ulcerative colitis. Colonoscopy is an inconvenient and uncomfortable test for most patients. In addition, it is not without serious risks of perforation, as well as risks which can be associated with sedation and analgesia given during the procedure. The use of biomarkers to aid in the diagnosis, subclassification, and monitoring of IBD is an ever expanding area. In this review, we have concentrated on noninvasive biomarkers of IBD, because these are more acceptable to patients and easier to perform in everyday clinical practice. We will first touch on those biomarkers currently well established and in wide clinical use, such as C-reactive protein, erythrocyte sedimentation rate. Faecal calprotectin and their use in the diagnosis of IBD. Following on, we will review more novel biomarkers and their use in subclassification and monitoring of IBD, including a variety of antibodies, genetics, and microRNAs, as well as touching on metabolomics.
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Birimberg-Schwartz L, Wilson DC, Kolho KL, Karolewska-Bochenek K, Afzal NA, Spray C, Romano C, Lionetti P, Hauer AC, Martinez-Vinson C, Veres G, Escher JC, Turner D. pANCA and ASCA in Children with IBD-Unclassified, Crohn's Colitis, and Ulcerative Colitis-A Longitudinal Report from the IBD Porto Group of ESPGHAN. Inflamm Bowel Dis 2016; 22:1908-14. [PMID: 27135480 DOI: 10.1097/mib.0000000000000784] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
INTRODUCTION No study to date has evaluated perinuclear antineutrophil cytoplasmic antibody (pANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) in pediatric inflammatory bowel disease-unclassified (IBDU) as compared with Crohn's colitis (CC) and ulcerative colitis (UC), which represent the diagnostic challenge. We aimed to explore the diagnostic utility of serology and to assess whether serology can predict disease severity in these subgroups. METHODS This was a multicenter retrospective longitudinal study including 406 children with inflammatory bowel diseases (IBD) from 23 centers affiliated with the Porto group of European Society of Pediatric Gastroenterology, Hepatology and Nutrition (mean age 10.5 ± 3.9, 54% males); 117 (29%) with CC, 143 (35%) with UC, and 146 (36%) with IBDU. Median follow-up period was 2.8 years (interquartile range, 1.6-4.2). RESULTS The most prevalent serologic profile in IBDU was pANCA-/ASCA- (41%), followed by pANCA+/ASCA- (34%) and pANCA-/ASCA+ (17%). pANCA-/ASCA+ differentiated well between CC versus IBDU (83% specificity, 96% positive predictive value [PPV]) and UC (97% specificity, 90% PPV) patients, albeit with a low negative predictive value (13% and 40%, respectively). pANCA+/ASCA- did not differentiate as well between IBD subgroups, but UC children with pANCA+/ASCA- had more often severe disease at diagnosis (36 [62%] versus 22 [38%], P = 0.033) and needed more often calcineurin inhibitors, biologics, or colectomy (25 [80%] versus 6 [20%], P = 0.026). In CC, double positivity for ASCA and not pANCA-/ASCA+ profile was associated with disease severity. CONCLUSIONS Serology may have some role in predicting disease course and outcomes in colonic IBD, but its routine use needs to be supported by more studies. Serology cannot routinely be recommended for differentiating between IBDU versus CC or UC as a sole diagnostic criterion given its low diagnostic utility.
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Affiliation(s)
- Liron Birimberg-Schwartz
- 1Shaare Zedek Medical Center, Jerusalem, Israel;2Child Life and Health, University of Edinburgh, United Kingdom;3University of Helsinki, Finland;4Department of Pediatric Gastroenterology, Medical University, Warsaw, Poland;5University Hospital Southampton, United Kingdom;6University Hospitals Bristol, Scotland, United Kingdom;7University of Messina, Italy;8University of Florence, Italy;9University Hospital for Pediatrics and Adolescent Medicine of the Medical University of Graz, Austria;10Department of Pediatric Gastroenterology and Nutrition, Robert Debré Hospital, Paris, France;11Semmelweis University, Budapest, Hungary;12Erasmus MC, Rotterdam, Zuid Holland, Netherlands; and13The Hebrew University of Jerusalem, Israel
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49
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Abstract
The genetic basis of antineutrophil cytoplasmic antibody, an important biomarker of inflammatory bowel disease (IBD), has never been thoroughly examined on a genome-wide scale. In this study, we performed a 2-stage genome-wide association study (GWAS) on antineutrophil cytoplasmic antibody in IBD cases. In the 2959 IBD cases in the discovery stage, we observed an association between a variant in the gene TNFRSF1B with antineutrophil cytoplasmic antibody level (rs5745994, minor allele frequency = 0.028, beta = 18.12, 95% CI, 11.82-24.22, P = 1.89 × 10). This association was replicated in an independent cohort of 419 IBD cases (beta = 16.91, 95% CI, 6.13-27.69, P = 2.38 × 10). With a Q-value of 0.036, we performed a fixed-effect meta-analysis for the association of rs5745994 in both cohorts and observed a stronger association signal (beta = 17.81, 95% CI, 12.36-23.25, P = 8.97 × 10). TNFRSF1B gene codes for tumor necrosis factor (TNF) receptor 2 (TNFR2), thereby we examined the reported TNFRSF1B variant with serum TNFR2 level. We observed a negative association with serum TNFR2 level being 8.23 EU/mL in carriers and 9.12 EU/mL in noncarriers (P = 0.033). This finding indicates the functional role of identified TNFRSF1B variant in IBD serology and may be reflective of the underlying biological mechanisms that determine clinical expression and/or response to certain therapies.
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Yu Q, Zhang S, Wang H, Zhang Y, Feng T, Chen B, He Y, Zeng Z, Chen M. TNFAIP6 is a potential biomarker of disease activity in inflammatory bowel disease. Biomark Med 2016; 10:473-83. [PMID: 27088253 DOI: 10.2217/bmm.16.9] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
AIM Ideal biomarkers are needed for evaluating the activity of inflammatory bowel disease (IBD). We aimed to investigate the value of TNFAIP6 as a biomarker. MATERIALS & METHODS Inflamed colonic samples and serum samples were collected from patients with Crohn's disease (CD), patients with ulcerative colitis (UC), and normal controls. SPSS 18.0 was used for statistical analysis. RESULTS Serum TNFAIP6 was higher in IBD patients than in normal controls and correlated with the inflammatory indicators. Compared with active patients, TNFAIP6 was decreased in both CD and UC patients in remission. Furthermore, TNFAIP6 concentrations consistent with TNF-α level, correlated well with disease location and extent of both CD and UC. CONCLUSION Serum TNFAIP6 may be a promising biomarker for evaluating the disease activity of IBD, demonstrating the diagnostic value in disease location differentiation.
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Affiliation(s)
- Qiao Yu
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shenghong Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Huiling Wang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yingfan Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ting Feng
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Baili Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yao He
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhirong Zeng
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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