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Adv Clin Chem. 2016;77:77-101. doi: 10.1016/bs.acc.2016.06.002. Epub 2016 Jun 30.

Autoimmunity in Crohn's Disease-A Putative Stratification Factor of the Clinical Phenotype.

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Institute of Biotechnology, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany; GA Generic Assays GmbH, Dahlewitz, Germany. Electronic address:
Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Inflammatory Bowel Disease Center, Charité Medical School, Humboldt-University of Berlin, Berlin, Germany.
Institute of Biotechnology, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany.
Institute of Immunology, Technical University Dresden, Dresden, Germany.
Medical Faculty of the Technical University Dresden, Dresden, Germany.


Inflammation in inflammatory bowel diseases (IBD) has been linked to a loss of tolerance to self-antigens suggesting the existence of autoantibodies in specific disease phenotypes. However, the lack of clearly defined autoantigenic targets has slowed down research. Genome-wide association studies have identified an impressive number of immune-related susceptibility loci for IBD with no clearly discernible pattern among them. Growing evidence supports the hypothesis that innate immune responses to a low-diversity and impaired gut microbiota may be of key importance in initiating and perpetuating chronic inflammation in IBD. Increasing evidence suggests that reduced microbial diversity and microbial-mucosal epithelium interaction (including adhesion and clearance) are critically involved in IBD pathogenesis. Along these lines the discovery of autoantigenic targets in Crohn's disease (CD) has refocused research in IBD on the possible role of autoimmune responses. The identification of the major zymogen granule membrane glycoprotein 2 (GP2) as an autoantigen in CD patients and its proposed role in the sensing of the microbiota lends credence to this trend. Loss of tolerance to GP2 occurs in up to 40% of patients with CD. Corresponding autoantibodies appear to be associated with distinct disease courses (types or phenotypes) in CD. Here, we critically review autoantibodies in CD for their impact on clinical practice and future IBD research. The immunomodulatory role of GP2 in innate and adaptive intestinal immunity is also discussed.


Crohn's disease; Inflammatory bowel diseases; Microbiota; Ulcerative colitis; Zymogen granule membrane glycoprotein 2

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