Antineutrophil cytoplasmic antibodies in T-cell receptor alpha-deficient mice with chronic colitis.
OBJECTIVE
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.
Mizoguchi
E
E
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Mizoguchi
A
A
Chiba
C
C
Niles
J L
JL
Bhan
A K
AK
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis* / Q000276:immunology; D001769:Blood / Q000276:immunology; D002457:Cell Extracts / Q000276:immunology; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D006657:Histones / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency*
D019268:Antibodies, Antineutrophil Cytoplasmic; D002457:Cell Extracts; D006657:Histones; D007070:Immunoglobulin A; D016693:Receptors, Antigen, T-Cell, alpha-beta