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

Gastroenterology. 1997 Dec;113(6):1828-35. doi: 10.1016/s0016-5085(97)70002-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Antineutrophil Cytoplasmic / analysis*
  • Antibodies, Antineutrophil Cytoplasmic / immunology
  • Blood / immunology
  • Cell Extracts / immunology
  • Chronic Disease
  • Colitis / immunology*
  • Colitis / metabolism*
  • Colitis / pathology
  • Colon / immunology
  • Colon / metabolism
  • Colon / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique, Indirect
  • Histones / immunology
  • Humans
  • Immunoglobulin A / metabolism
  • Lymph Nodes / immunology
  • Mesentery
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Neutrophils / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / deficiency*


  • Antibodies, Antineutrophil Cytoplasmic
  • Cell Extracts
  • Histones
  • Immunoglobulin A
  • Receptors, Antigen, T-Cell, alpha-beta