title: Reactivity against microsatellite instability-induced frameshift mutations in patients with inflammatory bowel disease.
abstract: OBJECTIVE
  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 MSI-induced 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Florian Kuehn, Ernst Klar, Anja Bliemeister, Michael Linnebacher, Department of General, Thoracic, Vascular and Transplantation Surgery, Molecular Oncology and Immunotherapy, University of Rostock, 18057 Rostock, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kuehn
authors.affiliation: Florian Kuehn, Ernst Klar, Anja Bliemeister, Michael Linnebacher, Department of General, Thoracic, Vascular and Transplantation Surgery, Molecular Oncology and Immunotherapy, University of Rostock, 18057 Rostock, Germany.
authors.forename: Ernst
authors.initials: E
authors.lastname: Klar
authors.affiliation: Florian Kuehn, Ernst Klar, Anja Bliemeister, Michael Linnebacher, Department of General, Thoracic, Vascular and Transplantation Surgery, Molecular Oncology and Immunotherapy, University of Rostock, 18057 Rostock, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Bliemeister
authors.affiliation: Florian Kuehn, Ernst Klar, Anja Bliemeister, Michael Linnebacher, Department of General, Thoracic, Vascular and Transplantation Surgery, Molecular Oncology and Immunotherapy, University of Rostock, 18057 Rostock, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebacher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D016368:Frameshift Mutation; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D008297:Male; D015122:Mercaptopurine / Q000031:analogs & derivatives / Q000627:therapeutic use; D053842:Microsatellite Instability; D008875:Middle Aged; D010641:Phenotype; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001324:Autoantigens; D005819:Genetic Markers; D007166:Immunosuppressive Agents; C488629:azathiopurine; D015122:Mercaptopurine
keywords: Frameshift peptides; Immune response; Inflammatory bowel diseas; Microsatellite-instability; Thiopurine