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

E Mizoguchi, A Mizoguchi, C Chiba, JL Niles, AK Bhan - Gastroenterology, 1997 - Elsevier
E Mizoguchi, A Mizoguchi, C Chiba, JL Niles, AK Bhan
Gastroenterology, 1997Elsevier
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 …
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. (Gastroenterology 1997 Dec;113(6):1828-35)
Elsevier