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 damage may promote further immune and inflammatory response. To investigate this, we studied the prevalence of antibodies against endothelial cells (AECA), ECM, and its major component collagen type IV in systemic vasculitis patients. Seventy-one percent of patients had AECA (binding 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 significantly 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 correlated with anti-collagen type IV (r = 0.45, P < 0.01). Positivity of cytoplasmic anti-neutrophil cytoplasmic antibodies (cANCA) was significantly lower in patients positive for anti-ECM and/or anti-collagen type IV antibodies (58% vs 11%, P = 0.048). AECA binding was partially reduced 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 ELISA. These results support the hypothesis that there is a humoral response against ECM components in addition to endothelial cells in systemic vasculitis patients which might have pathological significance in vascular damage.
Direskeneli
H
H
Lupus Arthritis Research Unit, Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
D'Cruz
D
D
Khamashta
M A
MA
Hughes
G R
GR
D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000097:blood / Q000378:metabolism*; D003094:Collagen / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D005109:Extracellular Matrix / Q000276:immunology*; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D014471:Umbilical Veins; D014657:Vasculitis / Q000097:blood / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D006493:Heparin; D003094:Collagen