Scientific Abstract

Proposal No.  IBD-0202
Principal Investigator: Xavier Bossuyt, M.D., Ph.D.
Applicant Organization: Katholieke Universiteit Leuven (Belgium)
Project Title: Identification of target antigens of antibodies in inflammatory bowel disease
Award Period: May 1, 2007 - December 31, 2009

Patients with inflammatory bowel disease display several antibodies. The antibodies are directed to a variety of antigens, such as food antigens [e.g., Saccharomyces cerevisiae], bacterial components [e.g., outer membrane porin C of Escherichia coli] or self-antigens [e.g., components of neutrophils or cells of the colon or the pancreas]. The most studied autoantibodies in IBD are anti-Saccharomyces cerevisiae antibodies (ASCA), atypical perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and anti-pancreas autoantibodies (PAB). ASCA are specific for Crohn’s disease (CD) and have a prevalence of 60 - 70% in CD, compared to 10 - 15% in ulcerative colitis (UC) and 0 - 5% in healthy subjects. pANCA have a prevalence of 50 - 80% in UC and 5 - 25% in CD. Anti-pancreas autoantibodies (PAB) are present in only 32% of CD and 23% of UC patients, but their absence in healthy subjects enlarges their potential in the diagnosis of IBD. ASCA are detected by ELISA (enzyme-linked immunosorbent assay). pANCA and PAB, however, are detected by indirect immunofluorescence, a technique with high interassay and interobserver variance. This greatly diminishes their diagnostic potential in IBD. Identification of the target antigens of these autoantibodies will allow the development of sensitive and specific solid-phase assays.

The aim of this project is the identification of the target antigens of pANCA and PAB and to search for novel autoantibodies in IBD. For this purpose, the innovative approach of protein microarray will be used. Sera of IBD patients and healthy controls will be probed against slides spotted with a large number of human proteins. This should allow identifying target antigens of antibodies present in the sera of patients and absent in controls. This should enable the development of solid-phase assays for the detection of novel (auto)antibodies. Their potential as a diagnostic marker will be evaluated.