T-CELL RESPONSES TO MYELOPEROXIDASE (MPO) AND PROTEINASE-3 (PR3) IN PATIENTS WITH SYSTEMIC VASCULITIS

T cell-mediated immune responses are likely to be important in the pat hogenesis of systemic vasculitis. However, identifying the T cells inv olved has proved difficult, and there are conflicting reports regardin g T cell proliferation in response to different autoantigens. Perinucl ear (P) and cytoplasmic (C) anti-neutrophil cytoplasmic antibodies (AN CA) are closely associated with systemic vasculitis, and are generally specific for MPO or PR3, respectively. We studied the proliferative r esponses to MPO and PR3 of peripheral blood mononuclear cells from pat ients with P-ANCA or C-ANCA specific for these antigens by ELISA. Thes e responses were compared with those of normal controls, and of diseas e controls with P- or C-ANCA not specific for MPO or PR3. The patient group as a whole showed significant T cell proliferation in response t o the autoantigens compared with controls (P=0.005). Cells from nine o f 13 P-ANCA-positive, anti-MPO-positive patients proliferated in respo nse to MPO, compared with five of 16 controls (P=0.04). Cells from fiv e of eight C-ANCA-positive, anti-PR3-positive patients proliferated in response to PR3, compared with two of 11 controls (P=0.05). These exp eriments demonstrate that patients with P-ANCA or C-ANCA possess T cel ls which respond to MPO or PR3, respectively. As in other autoimmune d iseases, responses to both antigens were also seen in a proportion of healthy controls. Further analysis of these responses will be importan t in understanding the pathogenesis of systemic vasculitis and in desi gning specific immunotherapy.