Direskeneli H, D'Cruz D, Khamashta M A, Hughes G R
Lupus Arthritis Research Unit, Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
Clin Immunol Immunopathol. 1994 Mar;70(3):206-10. doi: 10.1006/clin.1994.1030.
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.
内皮细胞和内皮下基质（ECM）参与血管炎的发病机制。血管损伤后ECM的暴露可能会促进进一步的免疫和炎症反应。为了对此进行研究，我们调查了系统性血管炎患者中抗内皮细胞抗体（AECA）、ECM及其主要成分IV型胶原的抗体的流行情况。71%的患者有AECA（结合指数，均值±标准差：64.8±48.1%；正常对照：8.9±6.9%，P<0.001）。与正常人相比，患者中的抗ECM和抗IV型胶原抗体也显著更高（抗ECM：28.6±29.6%对9.0±11.3%，P<0.002；抗IV型胶原：23.5±20.3%对8.1±9.1%，P<0.002）。AECA与抗ECM相关（r = 0.75，P<0.0001），但与抗IV型胶原不相关。抗ECM与抗IV型胶原相关（r = 0.45，P<0.01）。抗ECM和/或抗IV型胶原抗体阳性的患者中，胞浆型抗中性粒细胞胞浆抗体（cANCA）的阳性率显著更低（58%对11%，P = 0.048）。用ECM孵育后，AECA结合部分降低了25.1%。在AECA酶联免疫吸附测定中，加入肝素导致结合活性呈剂量依赖性抑制（19.2 - 30.6%）。这些结果支持这样的假说，即系统性血管炎患者除了针对内皮细胞外，还存在针对ECM成分的体液反应，这可能在血管损伤中具有病理意义。
