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 ulcerative 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 chronic colitis resembling human ulcerative colitis. Methods: Sera from 87 TCR-alpha(-/-) mice were tested for the presence of ANCAs by enzyme-linked immunosorbent assay against a human neutrophil extract and selected 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: Approximately 70% of sera from TCR-alpha(-/-) mice showed reactivity against human neutrophil extracts by enzyme-linked immunosorbent assay. Sixty percent of ANCA-positive sera showed a perinuclear reaction pattern. 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 autoantibodies was immunoglobulin A in the colon but not in the MLN and spleen. Conclusions: TCR-alpha(-/-) mice produce ANCAs. The ANCA (immunoglobulin A isotype)-producing B cells exist primarily in the diseased colonic mucosa of TCR alpha(-/-) mice.