原发性小血管炎和抗中性粒细胞胞浆抗体靶抗原的系列研究

抗中性粒细胞胞浆抗体(ANCA)是80年代中期发现的原发性小血管炎的特异性血清学诊断工具. ANCA相关小血管炎主要指韦格纳肉芽肿病(Wegener's granulomatosis, WG)、显微镜下型多血管炎(microscopic polyangiitis, MPA)和局灶节段坏死性肾小球肾炎(FSNGN).该类疾病为自身免疫性疾病,可累及全身多个脏器,肺、肾受累后多进展迅速,可危及患者生命或发展为肾衰竭.80年代我国对此类疾病认识不足,未诊断1例小血管炎引起的肾损害.10年来作者开展了对原发性小血管炎及ANCA靶抗原的系列研究.(1)80年代末在国内率先建立并逐步规范了ANCA的检测方法.(2)系统地研究并报道引起ANCA阳性小血管炎的一系列疾病并总结了相应的治疗方法.(3)发现了两种新的ANCA靶抗原:杀菌/通透性增高蛋白(BPI)和天青杀素(azurocidin).(4)开展了其他ANCA阳性疾病的靶抗原研究,证明组蛋白酶G是SLE-ANCA最为重要的靶抗原并证明抗组蛋白酶G抗体与狼疮肾炎的病理活动密切相关;同时在国内率先研究了溃疡性结肠炎的特异性靶抗原.上述工作填补了国内对ANCA相关小血管炎认识上的空白,提高了临床危重急症的救治水平,为进一步研究ANCA相关疾病的发病机制奠定了基础.

A serial study of small vessel vasculitides and target antigens of antineutrophil cytoplasmic antibodies (ANCA)

Anti neutrophil cytoplasmic antibodies (ANCA), discovered in the mid 1980s, are specific serological diagnostic tools for certain small vessel vasculitides, including Wegener's granulomatosus, microscopic polyangiitis and focal segmental necrotizing glomerulonephritis. ANCA associated vasculitis are systemic autoimmune disorders which often involve multi systems. After lung and kidney are affected, the diseases often rapidly progress to fatal lung hemorrhage and/or renal failure. In the 1980, ANCA associated vasculitis could not be diagnosed in China. The authors have conducted a serial study on ANCA associated vasculitis and on the identification of ANCA antigens.(1)To establish and gradually standardize ANCA methodology in China.(2)To study and report a variety of ANCA associated small vessel vasculitides and summarize appropriate therapies. (3) Two novel ANCA antigens wereidentified: bactericidal/permeability increasing protein (BPI) and azurocidin. (4)To investigate the target antigens of other ANCA associated diseases, cathepsin G was found to be the major ANCA antigen in SLE and the anti cathepsin G antibodies were closely correlated with renal pathologic activities; simultaneously, the specific ANCA target antigens for ulcerative colitis were also studied in Chinese patients. The above work has facilitated the recognition of ANCA associated vasculitis and enabled us to make early diagnosis and to commence therapy in time. It has also provided profound basis for further investigation of the pathogenesis of ANCA associated diseases.