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Publication : Antineutrophil cytoplasmic antibodies in T-cell receptor alpha-deficient mice with chronic colitis.

First Author  Mizoguchi E Year  1997
Journal  Gastroenterology Volume  113
Issue  6 Pages  1828-35
PubMed ID  9394722 Mgi Jnum  J:44797
Mgi Id  MGI:1101336 Doi  10.1016/s0016-5085(97)70002-7
Citation  Mizoguchi E, et al. (1997) Antineutrophil cytoplasmic antibodies in T-cell receptor alpha-deficient mice with chronic colitis. Gastroenterology 113(6):1828-35
abstractText  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 immuno-fluorescence 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.
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