ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES IN T-CELL RECEPTOR ALPHA-DEFICIENT MICE WITH CHRONIC COLITIS

Background & Aims: Antineutrophil cytoplasmic antibodies (ANCAs) have been detected in approximately 60% of sera from patients with ulcerati ve colitis. The aim of this study was to examine the presence of ANCAs and distribution of ANCA-producing B cells in the lymphoid tissue of T-cell receptor alpha-deficient (TCR-alpha(-/-)) mice that develop chr onic colitis resembling human ulcerative colitis. Methods: Sera from 8 7 TCR-alpha(-/-) mice were tested for the presence of ANCAs by enzyme- linked immunosorbent assay against a human neutrophil extract and sele cted antigens and by immunofluorescence study using human neutrophils. Enzyme-linked immunospot assay was used for detecting ANCA-producing cells from spleen, mesenteric lymph node (MLN), or colon. Results: App roximately 70% of sera from TCR-alpha(-/-) mice showed reactivity agai nst human neutrophil extracts by enzyme-linked immunosorbent assay. Si xty percent of ANCA-positive sera showed a perinuclear reaction patter n. By enzyme-linked immunospot, ANCA-producing cells were detected in MLN and colon and less often in the spleen of TCR-alpha(-/-) mice with chronic colitis. The predominant immunoglobulin isotype of these auto antibodies was immunoglobulin A in the colon but not in the MLN and sp leen. Conclusions: TCR-alpha(-/-) mice produce ANCAs. The ANCA (immuno globulin A isotype)-producing B cells exist primarily in the diseased colonic mucosa of TCR alpha(-/-) mice.