T cell reactivity to proteinase 3 and myeloperoxidase in patients with Wegener's granulomatosis (WG).
T cell-mediated immunity is hypothesized to play an important role in the pathogenesis of granulomatous inflammation and vasculitis as found in patients with WG. The antigenic specificities of those T cells remain, however, unknown. Anti-neutrophil cytoplasmic antibodies (ANCA) present in patients with WG are directed to proteinase 3 (PR3) and myeloperoxidase (MPO). In the present study we investigated the proliferative capacity of peripheral blood mononuclear cells (PBMC) from patients with WG and age- and sex-matched controls in response to the WG autoantigens PR3 and MPO. Possible mitogenic effects of active PR3 and toxic effects of active MPO were excluded by using heat-inactivated PR3 and MPO. Antigen-specific stimulation induced by these autoantigens was studied by using processed PR3 and MPO in the lymphocyte stimulation test (LST). Proliferation induced by processed antigen correlated with that by heat-inactivated free antigen. The general capacity to proliferate in response to mitogens and recall antigens did not differ between patients and controls. However, patients with WG who were or had been positive for PR3-ANCA (n = 17) responded more strongly to PR3 than to MPO and showed higher responses to PR3 compared with controls (n = 13). Within the PR3-ANCA group T cell proliferation did not correlate with ANCA titre. In a small group of patients with MPO-ANCA (n = 5) no differences were observed compared with controls for MPO-specific proliferation. The data presented demonstrate that autoreactive PR3-specific T cells are present in patients with WG. Their fine specificity and possible role in the pathogenesis of WG have to be defined in further studies.
Brouwer
E
E
Department of Clinical Immunology, University of Groningen, The Netherlands.
Stegeman
C A
CA
Huitema
M G
MG
Limburg
P C
PC
Kallenberg
C G
CG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic; D000918:Antibody Specificity; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology; D000941:Antigens / Q000494:pharmacology; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology*; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000201:enzymology / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D053146:Myeloblastin; D009195:Peroxidase / Q000276:immunology / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D000941:Antigens; D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin