Detection of cytotoxic CD13-specific autoantibodies in sera from patients with ulcerative colitis and Crohn's disease

Abstract

Recent evidence suggests an association between inflammatory bowel disease (IBD) and human cytomegalovirus (HCMV) infection, but the exact pathogenic role of HCMV in this disease remains unclear. HCMV infection has for a long time been known to be associated with various autoimmune manifestations and the formation of autoantibodies. Previous studies from our group have shown that HCMV is associated with a human protein, CD13 (aminopeptidase N) and that autoantibodies against this protein are frequently found in HCMV infected bone marrow transplant patients with chronic graft versus host disease. We have recently observed that 90% of IBD patients have an active HCMV infection. In this study, we examined the presence and cytotoxicity of CD13-specific autoantibodies in sera obtained from 28 patients with ulcerative colitis and 26 patients with Crohn's disease, and in sera obtained from healthy blood donors by using flow cytometric assays against mouse cells transfected with human CD13 or a microcytotoxicity assay against different CD13 positive human cells. Cytotoxic CD13-specific autoantibodies were identified in 66% of the sera obtained from HCMV-IgG positive patients with ulcerative colitis and in 58% of the sera obtained from HCMV-IgG positive patients with Crohn's disease, but not in control individuals. These cytotoxic autoantibodies may interfere with biological cell functions and could thereby contribute to the chronic inflammation in patients with IBD.