抗U1RNP抗体阳性患者血清抗人类肺动脉内皮细胞自身抗体的发现及其意义

目的检测抗U1RNP抗体阳性的自身免疫性疾病患者血清中抗人类肺动脉内皮细胞（HPAEC）自身抗体，并探讨其对肺动脉血管内皮损害的作用机制。方法通过RNA免疫沉降法筛选抗U1RNP抗体阳性血清，免疫印记分析检测血清中抗HPAEC自身抗体。通过流式细胞分析术，确定抗体靶抗原是否位于细胞的表面。用酶联免疫吸附试验（ELISA）测定含有该自身抗体IgG的HPAEC培养上清中活化T细胞调节的正常T细胞表达和分泌的因子（RANTES）的浓度。结果抗U1RNP抗体阳性血清中新发现一种同HPAEC表面相对分子质量31000抗原（HPA31抗原）反应的自身抗体，把含抗HPA31抗体的血清IgG分离纯化后加入HPAEC培养上清中，RANTES的量明显增加。结论自身免疫性疾病患者血清中存在与抗U1RNP抗体有一定相关的抗HPA31抗体，该抗体同细胞表面的靶抗原结合，可以活化HPAEC，促进RANTES产生及分泌，导致肺动脉血管内皮细胞的炎症损害。

Identification of autoantibodies against human pulmonary artery endothelial cells in anti-U1RNP antibody-positive patients with systemic autoimmune diseases and its significance in vascular damage

Objective To identify specific autoantibodies against human pulmonary artery endothelial cells(HPAEC)in sera of patients with systemic autoimmune diseases and investigate its possible role in vascu- lar damage.Methods Sera with anti-U_1RNP antibodies(Abs)were selected through RNA immunoprecipita- tion assay,and autoantibodies against autoantigens of HPAEC were detected by immunoblot.Flow cytomety analysis was used to reveal whether or not antigenic determinants of autoantibodies against HPAEC appeared on the surface of the cells.Chemokine secreted upon activation of normal T-cells and RANTES concentration in the culture supernatant after adding of IgG purified from anti-HPAEC Ab-positive sera was detected by ELISA.Results Autoantibodies that recognized specific autoantigens 31 000(HPA31)for HPAEC were newly identified.Antigenic determinants of HPA31 appeared on the surface of HPAEC.RANTES concentration in culture supernatant after adding of IgG purified from anti-HPA31 Ab-positive sera was significantly higher than anti-HPA31-negative sera.Conclusion Autoantibodies against HPAEC(anti-HPA31 Ab)exist in asso- ciation with anti-U_1RNP Ab-positve sera of patients with systemic autoimmune diseases.Anti-HPA31 Ab may activate HPAEC and stimulate RANTES.It may be involved in the process of inflammatory vascular damage.