AUTOANTIBODIES AGAINST ENDOTHELIAL-CELLS, EXTRACELLULAR-MATRIX, AND HUMAN COLLAGEN TYPE-IV IN PATIENTS WITH SYSTEMIC VASCULITIS

Endothelial cells and subendothelial matrix (ECM) are involved in the pathogenesis of vasculitis. Exposure of the ECM following vascular dam age may promote further immune and inflammatory response. To investiga te this, we studied the prevalence of antibodies against endothelial c ells (AECA), ECM, and its major component collagen type IV in systemic vasculitis patients. Seventy-one percent of patients had AECA (bindin g index, means +/- SD: 64.8 +/- 48.1%; normal controls: 8.9 +/- 6.9%, P < 0.001). Anti-ECM and anti-collagen type IV antibodies were also si gnificantly higher in patients compared to normals (anti-ECM: 28.6 +/- 29.6% vs 9.0 +/- 11.3%, P < 0.002; anti-collagen type IV: 23.5 +/- 20 .3% vs 8.1 +/- 9.1%, P < 0.002). AECA correlated with anti-ECM (r = 0. 75, P < 0.0001) but not with anti-collagen type IV. Anti-ECM correlate d with anti-collagen type IV (r = 0.45, P < 0.01). Positivity of cytop lasmic anti-neutrophil cytoplasmic antibodies (cANCA) was significantl y lower in patients positive for anti-ECM and/or anti-collagen type IV antibodies (58% vs 11%, P = 0.048). AECA binding was partially reduce d with ECM incubation by 25.1%. The addition of heparin caused a dose- dependent inhibition of binding activity (19.2-30.6%) in the AECA ELIS A. These results support the hypothesis that there is a humoral respon se against ECM components in addition to endothelial cells in systemic vasculitis patients which might have pathological significance in vas cular damage. (C) 1994 Academic Press, Inc.