Recurrent Goodpasture's disease secondary to a monoclonal IgA1-κ antibody autoreactive with the α1/α2 chains of type IV collagen
Recurrent Goodpasture's disease secondary to a monoclonal IgA1-κ antibody autoreactive with the α1/α2 chains of type IV collagen
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DOI：
10.1053/j.ajkd.2004.09.029
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发表时间：
2005-02-01
影响因子：
13.2
通讯作者：
Fervenza, FC
中科院分区：
文献类型：
--
作者：
Borza, DB;Chedid, MF;Fervenza, FC
Goodpasture病的特征是在抗肾小球基底膜（抗GBM）抗体存在下的新月体肾小球肾炎和肺出血。这种疾病通常由针对α 3（IV）胶原蛋白链的非胶原结构域的IgG自身抗体（Goodpasture自身抗原）介导。在极少数情况下，涉及伊加或IgM类的抗GBM抗体，但其特异性尚未确定，其靶抗原仍然未知。作者介绍了一例62岁男性患者，其患有单克隆IgA-κ抗体介导的抗GBM疾病，尽管进行了强化免疫抑制，但仍进展为终末期肾病。病人接受活体肾移植，但肺出血和新月体肾小球肾炎复发，导致移植物丢失2年后。间接免疫荧光发现存在循环伊加抗体与基底膜组分反应，通过酶联免疫吸附试验和Western印迹法鉴定为α 1/α 2（IV）胶原蛋白链。对胶原酶消化的敏感性表明伊加结合位于胶原结构域中的表位。这是第一例继发于自身反应性伊加抗体的肺出血性肾炎复发病例。第一次研究了与抗GBM疾病的发病机制有关的伊加抗体的特异性，鉴定了α 1/α 2（IV）胶原蛋白链作为致肾炎抗体的新靶点。
Goodpasture's disease is characterized by crescentic glomerulonephritis and lung hemorrhage in the presence of anti-glomerular basement membrane (anti-GBM) antibodies. This disease usually is mediated by IgG autoantibodies directed against the noncollagenous domain of the alpha 3(IV) collagen chain, the Goodpasture autoantigen. In rare cases, anti-GBM antibodies of IgA or IgM class are involved, but their specificity has not been determined, and their target antigen remains unknown. The authors present the case of a 62-year-old man with anti-GBM disease mediated by a monoclonal IgA-kappa antibody, which progressed to end-stage renal disease despite intensive immunosuppression. The patient underwent living-related kidney transplantation, but lung hemorrhage and crescentic glomerulonephritis recurred, causing the loss of the allograft 2 years later. Indirect immunofluorescence found the presence of circulating IgA antibodies reactive with a basement membrane component, identified by enzyme-linked immunoabsorbent assay and Western blot as the alpha 1/alpha 2(IV) collagen chains. Sensitivity to digestion with collagenase indicated that IgA bound to epitopes located in the collagenous domain. This is the first case of recurrent Goodpasture's disease secondary to an autoreactive IgA antibody. The specificity of an IgA antibody implicated in the pathogenesis of anti-GBM disease has been investigated for the first time, identifying the alpha 1/alpha 2(IV) collagen chains as a novel target for nephritogenic antibodies.