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Catalán-Serra I, Thorsvik S, Beisvag V, Bruland T, Underhill D, Sandvik AK, Granlund AVB. Fungal Microbiota Composition in Inflammatory Bowel Disease Patients: Characterization in Different Phenotypes and Correlation With Clinical Activity and Disease Course. Inflamm Bowel Dis 2024; 30:1164-1177. [PMID: 38103028 PMCID: PMC11219482 DOI: 10.1093/ibd/izad289] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Indexed: 12/17/2023]
Abstract
BACKGROUND There is growing evidence of the role of the mycobiome in inflammatory bowel disease (IBD). Variations within phenotypes and activity and with prognosis have been poorly studied. METHODS A total of 111 individuals were prospectively enrolled: 89 IBD patients (52 ulcerative colitis and 37 Crohn's disease [CD]) and 22 healthy individuals. Disease characteristics were collected and a fecal calprotectin >100 μg/mg was considered indicative of activity. A subset of patients was followed for 6 ± 2 years. Disease course was designated as either complicated or uncomplicated based on the need of intensified medication and/or surgery. ITS sequencing was performed targeting the ITS1 region. RESULTS We found lower Ascomycota/Basidiomycota ratio in IBD. Patients showed a marked increase in Candida dublinensis and Ca albicans and were depleted of Aspergillus rubrobrunneus and Penicillium brevicompactum (P ≤ .001) Saccharomyces was predominant in total colitis and Penicillium in proctitis. Several Penicillium species were depleted in total colitis vs proctitis. Ileal CD patients were enriched in Debaromyces hansenii and depleted of Ca tropicalis (P ≤ .001). Ca albicans was overrepresented in inflammatory (B1) vs fibrostenosing (B2) CD. Ca dublinensis was more abundant in active patients and correlated positively with fecal calprotectin and neutrophil gelatinase-associated lipocalin, while S pastorianus correlated inversely with activity. Ca sake was associated with complicated disease and increased abundance of Cryptococcus carnescens with the need for surgery in CD. CONCLUSIONS This study shows important differences in the mycobiome in IBD and within phenotypes. Selected fungal species were associated with complicated disease and the need of surgery in CD. This work adds to our understanding of the role of fungi in IBD, with potential clinical implications.
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Affiliation(s)
- Ignacio Catalán-Serra
- Centre of Molecular Inflammation Research, NTNU-Norwegian University of Science and Technology, Trondheim, Norway
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Gastroenterology, Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
| | - Silje Thorsvik
- Centre of Molecular Inflammation Research, NTNU-Norwegian University of Science and Technology, Trondheim, Norway
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Vidar Beisvag
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Torunn Bruland
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav’s University Hospital, Trondheim, Norway
| | - David Underhill
- Centre of Molecular Inflammation Research, NTNU-Norwegian University of Science and Technology, Trondheim, Norway
- Research Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Arne Kristian Sandvik
- Centre of Molecular Inflammation Research, NTNU-Norwegian University of Science and Technology, Trondheim, Norway
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav’s University Hospital, Trondheim, Norway
| | - Atle van Beelen Granlund
- Centre of Molecular Inflammation Research, NTNU-Norwegian University of Science and Technology, Trondheim, Norway
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav’s University Hospital, Trondheim, Norway
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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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Balderramo DC, Romagnoli PA, Granlund AVB, Catalan-Serra I. Fecal Fungal Microbiota (Mycobiome) Study as a Potential Tool for Precision Medicine in Inflammatory Bowel Disease. Gut Liver 2023; 17:505-515. [PMID: 37305948 PMCID: PMC10352062 DOI: 10.5009/gnl220537] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/06/2023] [Accepted: 02/15/2023] [Indexed: 06/13/2023] Open
Abstract
There is growing evidence of the role of fungal microbiota in the pathogenesis of inflammatory bowel disease (IBD). Fungi can exert direct pro-inflammatory effects or modify the bacterial composition via interkingdom interactions. Although several studies have demonstrated alterations in the fecal fungal microbiota composition in IBD, there is a wide variation in the mycobiome in different populations, with no definite pattern that can define the mycobiome in IBD having yet been identified. Recent work has suggested that characterizing the fecal fungal composition may influence therapeutic decisions and help to predict outcomes in a subset of IBD patients. In this study, we review the current literature on the emerging role of the fecal mycobiome as a potential tool for precision medicine in IBD.
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Affiliation(s)
- Domingo C. Balderramo
- Department of Gastroenterology, Private Hospital Medical Center of Cordoba S.A., Cordoba, Argentina
| | - Pablo Alberto Romagnoli
- Universitarian Institute for Biomedical Sciences of Cordoba (IUCBC), Translational Medicine Research Center "Severo R. Amuchastegui" (CIMETSA). G.V. Medical Research Institute "Mercedes and Martin Ferreyra" (INIMEC-CONICET-UNC), Cordoba, Argentina
| | - Atle van Beelen Granlund
- Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav’s University Hospital, Trondheim, Norway
- Department of Clinical and Molecular Medicine (IKOM), NTNU-Norwegian University of Science and Technology, Trondheim, Norway
- Centre of Molecular Inflammation Research, NTNU-Norwegian University of Science and Technology, Trondheim, Norway
| | - Ignacio Catalan-Serra
- Department of Clinical and Molecular Medicine (IKOM), NTNU-Norwegian University of Science and Technology, Trondheim, Norway
- Centre of Molecular Inflammation Research, NTNU-Norwegian University of Science and Technology, Trondheim, Norway
- Department of Medicine, Gastroenterology, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
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The Role of Glycosylation in Inflammatory Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1325:265-283. [PMID: 34495540 DOI: 10.1007/978-3-030-70115-4_13] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The diversity of glycan presentation in a cell, tissue and organism is enormous, which reflects the huge amount of important biological information encoded by the glycome which has not been fully understood. A compelling body of evidence has been highlighting the fundamental role of glycans in immunity, such as in development, and in major inflammatory processes such as inflammatory bowel disease, systemic lupus erythematosus and other autoimmune disorders. Glycans play an instrumental role in the immune response, integrating the canonical circuits that regulate innate and adaptive immune responses. The relevance of glycosylation in immunity is demonstrated by the role of glycans as important danger-associated molecular patterns and pathogen-associated molecular patterns associated with the discrimination between self and non-self; also as important regulators of the threshold of T cell activation, modulating receptors signalling and the activity of both T and other immune cells. In addition, glycans are important determinants that regulate the dynamic crosstalk between the microbiome and immune response. In this chapter, the essential role of glycans in the immunopathogenesis of inflammatory disorders will be presented and its potential clinical applications (diagnosis, prognosis and therapeutics) will be highlighted.
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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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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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Musatti A, Rollini M, Sambusiti C, Manzoni M. Zymomonas mobilis: biomass production and use as a dough leavening agent. ANN MICROBIOL 2014. [DOI: 10.1007/s13213-014-0997-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Utility of fecal and serum anti-Saccharomyces cerevisiae antibodies in the diagnosis of Crohn's disease-like condition of the pouch. Int J Colorectal Dis 2012; 27:1455-63. [PMID: 22430887 DOI: 10.1007/s00384-012-1444-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/29/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND Fecal antibodies against bacterial products may directly reflect the interaction between luminal bacteria and mucosal immunity, and assays for these antibodies may be clinically useful in the diagnosis and differential diagnosis of Crohn's disease-like (CDL) condition of the pouch. AIMS This study aims to evaluate stool and serum anti-Saccharomyces cerevisiae antibodies (ASCA) in normal and diseased pouches, to assess the correlation between ASCA levels and endoscopic disease activity, and to ascertain the diagnostic utility of ASCA for CDL of the pouch. METHODS One hundred eighty-nine patients with ileal pouches were prospectively enrolled and corresponding serum and pouch aspirate samples were collected. Fecal and serum ASCA levels were measured with enzyme-linked immunosorbent assay in a blinded fashion. Statistical analysis was then conducted using the signed rank test, Spearman correlation coefficients, and analysis of variance. RESULTS Forty-three patients (22.8 %) had irritable pouch syndrome or normal pouches, 74 (39.2 %) had pouchitis/cuffitis, 52 (27.5 %) had CDL, 9 (4.8 %) had familial adenomatous polyposis, and 11 (5.8 %) had surgical complications of the pouch. Receiver operating characteristic curves to distinguish CDL from other categories of pouch dysfunction had an area under the curve (AUC) of 0.608 for fecal ASCA and an AUC of 0.517 for serum ASCA. Neither fecal nor serum ASCA correlated with endoscopic disease activity scores. There was a significant difference in the mean values of fecal ASCA between inflammatory and fistulizing CDL (0.27 vs. 0.03 ELISA units/ml, P < 0.05). CONCLUSIONS Fecal ASCA appears to be better than serum ASCA in differentiating CDL from other pouch disorders, although this distinction may be of limited clinical utility.
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Zhang Z, Li C, Zhao X, Lv C, He Q, Lei S, Guo Y, Zhi F. Anti-Saccharomyces cerevisiae antibodies associate with phenotypes and higher risk for surgery in Crohn's disease: a meta-analysis. Dig Dis Sci 2012; 57:2944-54. [PMID: 22669207 DOI: 10.1007/s10620-012-2244-y] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2011] [Accepted: 05/03/2012] [Indexed: 12/22/2022]
Abstract
BACKGROUND Recent studies suggested that anti-Saccharomyces cerevisiae antibody (ASCA) status was associated with diagnostic findings, stratified classification phenotypes, disease activity and clinical course of Crohn's disease (CD). However, the relationship between ASCA status and phenotypes of CD remains controversial in these studies. AIMS The purpose of this study was to evaluate whether ASCA status is associated with the phenotypes and the risk of surgery in diverse populations in CD. METHODS We conducted a meta-analysis of studies assessing the association of ASCA status with phenotypes and risk of surgery in CD. Three independent reviewers undertook data extraction. We pooled odds ratios separately for the cohort and case-control studies. RESULTS We identified ten cohort studies (n = 2,365) and 14 case-control studies (n = 1,887) that investigated the association of ASCA status with phenotypes and risk of surgery in CD. The meta-analysis of the cohort studies showed significant association between the ASCA-positive status and higher risk of early-onset age (OR 2.25, 95 % CI 1.41-3.57, P < 0.001), ileal involvement disease (1.70, 1.05-2.77, P = 0.03), complicated disease behavior (2.09, 1.71-2.57, P < 0.001), perianal disease (1.49, 1.14-1.94, P = 0.004), and risk for surgery (1.61, 1.29-2.01, P < 0.001). Meta-analysis of the case-control studies also showed a significantly higher risk in ileal involvement disease (1.77, 1.25-2.49, P = 0.001), complicated disease behavior (2.13, 1.70-2.68, P < 0.001), perianal disease (1.96, 1.38-2.78, P < 0.001), and risk for surgery (1.71, 1.17-2.49, P = 0.005), except for the early-onset age (1.16, 0.80-1.69, P = 0.44). CONCLUSIONS This meta-analysis indicated that positive ASCA status is a risk factor for early-onset age, ileal involvement, complicated behavior, perianal disease and requirement for surgery in CD.
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Affiliation(s)
- Zhaoxia Zhang
- Guangdong Province Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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Clinical significance and prevalence of anti-Saccharomyces cerevisiae antibody in Chinese patients with primary biliary cirrhosis. Clin Exp Med 2012; 13:245-50. [DOI: 10.1007/s10238-012-0207-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2012] [Accepted: 08/13/2012] [Indexed: 01/28/2023]
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Mpofu CM, Campbell BJ, Subramanian S, Marshall-Clarke S, Hart CA, Cross A, Roberts CL, McGoldrick A, Edwards SW, Rhodes JM. Microbial mannan inhibits bacterial killing by macrophages: a possible pathogenic mechanism for Crohn's disease. Gastroenterology 2007; 133:1487-98. [PMID: 17919633 DOI: 10.1053/j.gastro.2007.08.004] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2006] [Accepted: 07/19/2007] [Indexed: 01/12/2023]
Abstract
BACKGROUND & AIMS Crohn's disease (CD) is mimicked by inherited phagocyte disorders and is associated with circulating antibodies against yeast mannan (anti-Saccharomyces cerevisiae antibody; ASCA). We speculated that mannans might impair phagocyte function. METHODS S cerevisiae mannan was assessed for its effects on human peripheral blood neutrophils, adherent monocytes, and monocyte-derived macrophages (MDM). RESULTS Mannan caused dose-related increased survival of CD Escherichia coli HM605 within adherent monocytes from 24% +/- 10.5% (control) to 114% +/- 22.7% with mannan 1 mg/mL at 2 hours (mean +/- SEM, n = 9; P = .0002). Electron microscopy showed E coli HM605 surviving and probably replicating within macrophage vesicles. Mannan (1 mg/mL) inhibited the respiratory burst in neutrophils and monocytes (both P = .002) and bacterial killing within MDM (P < .001). E coli survival was increased within macrophages from TLR4(-/-) (126% +/- 3.5% survival at 2 hours) and MyD88(-/-) (134.8% +/- 6.5%) mice compared with wild-type mice (both P < .0001). Mannan had no additional effect, showing that TLR4 and MyD88 are involved in bacterial killing by macrophages and its inhibition by mannan. Putative CD-associated micro-organisms were screened for the ASCA mannan epitope by Galanthus nivalis lectin (GNA) blotting. ASCA epitope was expressed by Candida albicans and Mycobacterium paratuberculosis but not by Mycobacterium tuberculosis or E coli. Supernatants from M paratuberculosis culture inhibited killing of E coli HM605 by adherent human monocytes and murine macrophages. The inhibitory activity was removed by GNA-affinity chromatography. CONCLUSIONS Suppression of mucosal phagocyte function by microbial mannans, possibly of Mycobacterial origin, may contribute to CD pathogenesis.
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Affiliation(s)
- Chiedzo M Mpofu
- Division of Gastroenterology, School of Clinical Science, University of Liverpool, Liverpool, United Kingdom
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Toumi D, Mankaï A, Belhadj R, Ghedira-Besbes L, Jeddi M, Ghedira I. Anti-Saccharomyces cerevisiae antibodies in coeliac disease. Scand J Gastroenterol 2007; 42:821-6. [PMID: 17558905 DOI: 10.1080/00365520601154996] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To evaluate, retrospectively, the frequency of anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with coeliac disease. MATERIAL AND METHODS ASCA, IgG and IgA were determined by ELISA in sera of 238 coeliac patients. The patients were divided into three groups: group I - 125 untreated patients; group II - 42 patients under a strict gluten-free diet (GFD); and group III - 71 patients who did not comply with a GFD. Sera of 80 healthy blood donors served as controls. RESULTS The frequency of ASCA (IgG or IgA) was significantly higher in untreated coeliac patients than in the control group (27.2% versus 3.7%, p=10(-5)). In 238 coeliac patients, the frequency of ASCA was significantly higher in adults than in children (35.4% versus 21.1%, p=0.01). In group III, the frequency of ASCA was significantly higher in adults than in children (60% versus 26.1%, p=0.004). In 238 coeliac patients, ASCA IgG were significantly more frequent than ASCA IgA in both children (19% versus 6.3%, p=0.001) and adults (33.3% versus 12.5%, p=5.10(-4)). In children, ASCA IgG were negative in group II and positive in 20% of group I (p=0.01). In adults, the frequency of ASCA IgG was also significantly lower in group II than in group I (9.5% versus 34%, p=0.03). CONCLUSIONS A high frequency of ASCA has been found in coeliac patients. The frequency of ASCA was not statistically different between patients with successful adherence to GFD and healthy controls.
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Affiliation(s)
- Dorsaf Toumi
- Research Unit (03UR/07-02), Faculty of Pharmacy, Monastir, Tunisia
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Cucchiara S, Latiano A, Palmieri O, Staiano AM, D'Incà R, Guariso G, Vieni G, Rutigliano V, Borrelli O, Valvano MR, Annese V. Role of CARD15, DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases. World J Gastroenterol 2007; 13:1221-1229. [PMID: 17451203 PMCID: PMC4146997 DOI: 10.3748/wjg.v13.i8.1221] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2006] [Revised: 12/01/2006] [Accepted: 01/12/2007] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predisposition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS Two hundred patients with Crohn's disease (CD), 186 ulcerative colitis (UC) patients, 434 parents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more common in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an increased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was more frequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric onset of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.
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Affiliation(s)
- S Cucchiara
- Clinica Pediatrica, Università L Sapienza, Roma, Italy
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Reese GE, Constantinides VA, Simillis C, Darzi AW, Orchard TR, Fazio VW, Tekkis PP. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol 2006; 101:2410-22. [PMID: 16952282 DOI: 10.1111/j.1572-0241.2006.00840.x] [Citation(s) in RCA: 176] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIMS The aim of this study was to assess the diagnostic precision of antiSaccharomyces cerevisiae (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) in inflammatory bowel disease (IBD) and evaluate their discriminative ability between ulcerative colitis (UC) and Crohn's disease (CD). METHODS Meta-analysis of studies reporting on ASCA and pANCA in IBD was performed. Sensitivity, specificity, and likelihood ratios (LR+, LR-) were calculated for different test combinations for CD, UC, and for IBD compared with controls. Meta-regression was used to analyze the effect of age, DNAse, colonic CD, and assay type. RESULTS Sixty studies comprising 3,841 UC and 4,019 CD patients were included. The ASCA+ with pANCA- test offered the best sensitivity for CD (54.6%) with 92.8% specificity and an area under the ROC (receiver operating characteristic) curve (AUC) of 0.85 (LR+ = 6.5, LR- = 0.5). Sensitivity and specificity of pANCA+ tests for UC were 55.3% and 88.5%, respectively (AUC of 0.82; LR+ = 4.5, LR- = 0.5). Sensitivity and specificity were improved to 70.3% and 93.4% in a pediatric subgroup when combined with an ASCA- test. Meta-regression analysis showed decreased diagnostic precision of ASCA for isolated colonic CD (RDOR = 0.3). CONCLUSIONS ASCA and pANCA testing are specific but not sensitive for CD and UC. It may be particularly useful for differentiating between CD and UC in the pediatric population.
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Affiliation(s)
- George E Reese
- Department of Biosurgery and Surgical Technology, Imperial College London, St Mary's Hospital, London, United Kingdom
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Granito A, Zauli D, Muratori P, Muratori L, Grassi A, Bortolotti R, Petrolini N, Veronesi L, Gionchetti P, Bianchi FB, Volta U. Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic antibodies in coeliac disease before and after gluten-free diet. Aliment Pharmacol Ther 2005; 21:881-887. [PMID: 15801923 DOI: 10.1111/j.1365-2036.2005.02417.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies are markers of Crohn's disease and ulcerative colitis respectively. AIM To determine the prevalence of anti-S. cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies in a large series of coeliac disease patients before and after gluten free diet, and to correlate anti-S. cerevisiae-positivity with intestinal mucosal damage. METHODS One hundred and five consecutive coeliac disease patients and 141 controls (22 ulcerative colitis, 24 Crohn's disease, 30 primary sclerosing cholangitis, 15 postenteritis syndrome, 50 blood donors) were tested for anti-S. cerevisiae by enzyme-linked immunosorbent assay and for perinuclear anti-neutrophil cytoplasmic autoantibodies by indirect immunofluorescence. RESULTS In coeliac disease anti-S. cerevisiae (immunoglobulin G and/or immunoglobulin A) were slightly less frequent (59%) than in Crohn's disease (75%, P = 0.16) and significantly more frequent than in ulcerative colitis (27%), primary sclerosing cholangitis (30%), postenteritis syndrome (26%) and blood donors (4%) (P = 0.009, P = 0.0002, P = 0.025, P < 0.0001). No correlation was found between anti-S. cerevisiae and degree of mucosal damage. Perinuclear anti-neutrophil cytoplasmic autoantibodies were detected only in one coeliac. After gluten free diet the disappearance of anti-S. cerevisiae-immunoglobulin A (93%) was more frequent than that of immunoglobulin G (17%, P = 0.0001); perinuclear anti-neutrophil cytoplasmic autoantibodies disappeared in the only coeliac positive at diagnosis. CONCLUSION More than half of untreated coeliacs are anti-S. cerevisiae-positive irrespective of the severity of mucosal damage. Differently from immunoglobulin A, anti-S. cerevisiae-immunoglobulin G persisted in more than 80% after gluten free diet. The high prevalence of anti-S. cerevisiae in coeliac disease suggests that they may be the effect of a non-specific immune response in course of chronic small bowel disease.
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Affiliation(s)
- A Granito
- Department of Internal Medicine, Alma Mater Studiorum, University of Bologna, Policlinico Sant'Orsola-Malpighi, 40138 Bologna, Italy.
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