Reactivity against microsatellite instability-induced frameshift mutations in patients with inflammatory bowel disease

• Published in: World journal of gastroenterology : WJG 2015-01, Vol.21 (1), p.221-228
• Main Authors: Kuehn, Florian, Klar, Ernst, Bliemeister, Anja, Linnebacher, Michael
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Autoantigens - genetics; Autoantigens - immunology; bowel; Case Control Study; Case-Control Studies; dise; Female; Frameshift Mutation; Genetic Markers; Genetic Predisposition to Disease; Humans; Immunosuppressive Agents - therapeutic use; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - immunology; Male; Mercaptopurine - analogs & derivatives; Mercaptopurine - therapeutic use; Microsatellite Instability; Microsatellite-instability; Inflammatory; Middle Aged; Phenotype; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Time Factors; Treatment Outcome; Young Adult
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v21.i1.221

AIM: To analyze the cellular immune response towards microsatellite-instability(MSI)-induced frameshift-peptides(FSPs) in patients suffering from inflammatory bowel disease(IBD) with and without thiopurine-based immunosuppressive treatment.METHODS: Frequencies of peripheral blood T cell responses of IBD patients(n = 75) against FSPs derived from 14 microsatellite-containing candidate genes were quantified by interferon-γ enzyme-linked immunospot.T cells derived from 20 healthy individuals served as controls.RESULTS: Significant T cell reactivities against MSIinduced FSPs were observed in 59 of 75 IBD patients(78.7%).This was significantly more as we could observe in 20 healthy controls(P = 0.001).Overall,the reactivity was significantly influenced by thiopurine treatment(P = 0.032) and duration of disease(P = 0.002) but not by duration or cumulative amount of thiopurine therapy(P = 0.476).Unexpected,15 of 24(62.5%) IBD patients without prior thiopurine treatment also showed increased FSP-specific immune responses(P = 0.001).CONCLUSION: These findings propose FSPs as potential novel class of inflammation-associated antigens and this in turn may have implications for screening,diagnosis as well as clinical management of patients suffering from IBD and other inflammatory conditions.