Association of Epitope Spreading of Antiglomerular Basement Membrane Antibodies and Kidney Injury
Association of Epitope Spreading of Antiglomerular Basement Membrane Antibodies and Kidney Injury
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抗肾小球基底膜抗体表位扩散与肾损伤的关联。
DOI：
10.2215/cjn.05140512
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发表时间：
2013-01-01
影响因子：
9.8
通讯作者：
Zhao, Ming-hui
中科院分区：
文献类型：
--
作者：
Chen, Jun-liang;Hu, Shui-yi;Zhao, Ming-hui
背景与目的抗肾小球基底膜自身抗体在抗肾小球基底膜疾病中具有致病性，其主要抗原表位为E-A和E-B，位于ⅳ型胶原蛋白α - 3链上。本研究对抗肾小球基底膜自身抗体的表位谱进行了研究，旨在确定表位特异性与肾损伤之间的关系。将108例临床资料完整的抗肾小球基底膜病患者根据肾功能情况分为3组：轻度组（n=20），血清肌酐= 6.8 mg/dl；ELISA法测定抗体的表位谱，并分析其与肾损害的关系。在病程中对40例患者进行连续血清检测。结果E-A和E-B的识别率分别为79.6%和72.2%。E-A、E-B反应在轻度组最低，在中度组较高（E-A: 35.0%比81.8%，P=0.002; E-B: 15.0%比68.2%，P=0.001）。以重症组最高（E-A: 92.4%， P=0.31; E-B: 90.9%， P=0.02）。肾损伤与E-A、E-B反应密切相关。多因素Cox回归分析显示，E-B反应是肾功能衰竭的独立危险因素（危险比=6.91，P=0.02）。各群体对非e - ab的认知度仍然很低。系列血清样品表位谱未见扩增。结论在人抗肾小球基底膜病发病前可能存在分子内表位扩散。对E-A和E-B的自身免疫，尤其是E-B对肾功能障碍至关重要。中国临床医学杂志，2013,31(2):551 - 558。doi: 10.2215 / CJN.05140512
Background and objectives Antiglomerular basement membrane autoantibodies are pathogenic in antiglomerular basement membrane disease with two major epitopes, E-A and E-B, on alpha 3 chain of type IV collagen. This study investigated the epitope spectrum of antiglomerular basement membrane autoantibodies, aiming to identify the association between epitope specificity and kidney injury.Design, setting, participants, & measurements All 108 patients with antiglomerular basement membrane disease and complete clinical data were divided into three groups according to renal dysfunction: mild group (n=20) with serum creatitine = 6.8 mg/dl. Epitope spectrums of antibodies were determined by ELISA, and their associations with kidney damage were analyzed. Sequential serum samples in 40 patients were examined during disease courses.Results E-A and E-B were recognized in 79.6% and 72.2% of patients, respectively. E-A and E-B reactions were the lowest in the mild group and higher in the moderate group (E-A: 35.0% versus 81.8%, P=0.002; E-B: 15.0% versus 68.2%, P=0.001). They were the highest in the severe group (E-A: 92.4%, P=0.31; E-B: 90.9%, P=0.02). Close association was observed between renal injury and E-A and E-B reactions. Multivariate Cox regression analysis showed that E-B reaction was an independent risk factor for renal failure (hazard ratio=6.91, P=0.02). The recognition for non-E-AB remained low among groups. No augmentation of epitope spectrum was shown in serial serum samples.Conclusions Intramolecular epitope spreading might occur before the onset of human antiglomerular basement membrane disease. The autoimmunity to E-A and E-B, especially E-B, was crucial for kidney dysfunction. Clin J Am Soc Nephrol 8: 51-58, 2013. doi: 10.2215/CJN.05140512