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Autoantibodies against the bactericidal/permeability‐increasing protein from inflammatory bowel disease patients can impair the antibiotic activity of bactericidal/permeability‐increasing protein
Bactericidal/permeability‐increasing protein (BPI) is an antineutrophil cytoplasmic autoantibody (ANCA) target antigen in inflammatory bowel disease (IBD). The aim of this study was to characterize binding regions of BPI‐autoantibodies and to analyze their ability to block the antibiotic effect of BPI. Sera of 24 ulcerative colitis and Crohn's disease patients were examined in indirect immuno‐fluorescence, ANCA enzyme‐linked immunosorbent assay (ELISA), and by epitope mapping with 13mer peptides and Western blot for presence of BPI‐autoantibodies. IgG preparations were used to determine inhibition of BPI's antimicrobial function by BPI‐autoantibodies in a bacterial growth inhibition assay. BPI‐autoantibodies were detected by ELISA in 18/24 patients. Epitope mapping and western blotting revealed an additional 3 patients with BPI‐autoantibodies. IgG preparations of all patients with Crohn's disease and 9 of 12 ulcerative colitis patients could inhibit the antibiotic function of BPI in vitro as compared with healthy control subjects. Inhibiting BPI‐autoantibodies correlated with extraintestinal manifestations, peripheral blood leukocyte counts, and anemia. BPI‐autoantibodies recognizing the N‐terminal portion were associated with greater mucosal damage and intestinal extent of disease. BPI is a frequent target antigen of autoantibodies in ulcerative colitis and Crohn's disease. Inhibition of the antibiotic function mediated by the N‐terminal region of BPI by these autoantibodies may contribute to a proinflammatory environment in IBD patients.