title: T lymphocyte responses to anti-neutrophil cytoplasmic autoantibody (ANCA) antigens are present in patients with ANCA-associated systemic vasculitis and persist during disease remission.
abstract: ANCA with specificity for myeloperoxidase (MPO) and proteinase 3 (PR3) are present in patients with systemic vasculitis. The aim of this work was to determine whether such patients have T cell responses to these antigens and whether these responses are related to disease activity. Peripheral blood lymphocytes from 45 patients and 19 controls were cultured with ANCA antigens and proliferation measured. The antigens used were heat-inactivated (HI) MPO, HI PR3, native (non-HI) PR3, HI whole alpha-granules, and 25 overlapping peptides covering the entire PR3 sequence. Significant responses to both whole PR3 preparations were seen from patient and control groups, and to the alpha-granules from the patient group. Patients responded at all stages of disease: active, remitting, treated or untreated. Only two patients responded significantly to MPO. Responses were significantly higher with the patient group than the control group to all four whole ANCA antigens. Responses to those PR3 peptides containing epitopes known to be recognized by ANCA were detected from one patient. Thus, these studies demonstrate that T cells from vasculitis patients can proliferate to PR3 and occasionally to associated ANCA antigens. Further, responses may persist even after disease remission has been achieved.
authors.affiliation: Renal Immunobiology, University of Birmingham, UK.
authors.forename: W J
authors.initials: WJ
authors.lastname: King
authors.forename: C J
authors.initials: CJ
authors.lastname: Brooks
authors.forename: R
authors.initials: R
authors.lastname: Holder
authors.forename: P
authors.initials: P
authors.lastname: Hughes
authors.forename: D
authors.initials: D
authors.lastname: Adu
authors.forename: C O
authors.initials: CO
authors.lastname: Savage
mesh_terms: D000595:Amino Acid Sequence; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D053146:Myeloblastin; D009195:Peroxidase / Q000276:immunology*; D012697:Serine Endopeptidases / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001324:Autoantigens; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin