Yu F, Zhao M-H, Zhang Y-K, Zhang Y, Wang H-Y
Institutes Renal Division and Institute of Nephrology, Peking University First Hospital, Beijing, China.
Clin Exp Immunol. 2005 Mar;139(3):569-74. doi: 10.1111/j.1365-2249.2005.02725.x.
Increasing evidence has demonstrated that propylthiouracil (PTU) could induce ANCA positive vasculitis. However, our previous work has suggested that only one-fifth of the PTU-induced ANCA positive patients had clinical vasculitis and so the mechanism is not clear. Anti-endothelial cell antibodies (AECA) have been implicated in the pathogenesis of various vasculitides, including primary ANCA positive systemic vasculitis. The purpose of this study is to investigate the prevalence of AECA and their possible role in the pathogenesis of patients with PTU-induced ANCA positive vasculitis. Sera from 11 patients with PTU-induced ANCA positive vasculitis at both active and quiescent phases, and sera from 10 patients with PTU-induced ANCA but without clinical vasculitis, were studied. Sera from 30 healthy blood donors were collected as normal controls. Soluble proteins from 1% Triton-100 extracted in vitro cultured human umbilical vein endothelial cells were used as antigens and an immunoblotting technique was performed to determine the presence of AECA, and their specific target antigens were identified. In patients with PTU-induced ANCA positive vasculitis, 10 of the 11 patients in an active phase of disease were serum IgG-AECA positive and six protein bands of endothelial antigens could be blotted (61 kD, 69 kD, 77 kD, 85 kD, 91 kD and 97 kD). However, in the quiescent phase, seven of the 10 positive sera turned negative. None of the ANCA positive but vasculitis negative patients or normal controls were AECA positive. In conclusion, AECA could be found in sera from patients with PTU-induced ANCA positive vasculitis and were associated more closely with vasculitic disease activity.
越来越多的证据表明,丙硫氧嘧啶(PTU)可诱发抗中性粒细胞胞浆抗体(ANCA)阳性血管炎。然而,我们之前的研究表明,PTU诱发的ANCA阳性患者中只有五分之一有临床血管炎表现,因此其机制尚不清楚。抗内皮细胞抗体(AECA)与包括原发性ANCA阳性系统性血管炎在内的各种血管炎的发病机制有关。本研究旨在调查AECA的患病率及其在PTU诱发的ANCA阳性血管炎患者发病机制中的可能作用。研究了11例PTU诱发的ANCA阳性血管炎患者在活动期和静止期的血清,以及10例PTU诱发的ANCA阳性但无临床血管炎患者的血清。收集30名健康献血者的血清作为正常对照。用1% Triton - 100从体外培养的人脐静脉内皮细胞中提取的可溶性蛋白作为抗原,采用免疫印迹技术检测AECA的存在,并鉴定其特异性靶抗原。在PTU诱发的ANCA阳性血管炎患者中,11例疾病活动期患者中有10例血清IgG - AECA阳性,可印迹出6条内皮抗原蛋白带(61 kD、69 kD、77 kD、85 kD、91 kD和97 kD)。然而,在静止期,10例阳性血清中有7例转为阴性。ANCA阳性但血管炎阴性的患者或正常对照均无AECA阳性。总之,PTU诱发的ANCA阳性血管炎患者血清中可检测到AECA,且与血管炎疾病活动度密切相关。