Cui Zhao, Zhao Ming-Hui
Renal Division and Institute of Nephrology, Peking University First Hospital, Beijing 100034, P.R. China.
Clin Immunol. 2005 Jul;116(1):77-82. doi: 10.1016/j.clim.2005.02.016.
Anti-glomerular basement membrane (GBM) antibody-mediated diseases are characterized by the binding of autoantibodies to GBM, leading to rapidly progressive glomerulonephritis that often results in irreversible loss of renal function. The nephrotoxic potential of anti-GBM antibodies has been demonstrated in animal experiments. We questioned whether high avidity leads to persistent deposition of anti-GBM antibodies, thereby perpetuating inflammation and renal damage. To address the hypothesis, sera from 32 patients and serial samples from 11 patients with anti-GBM disease were collected. Purified bovine alpha chain non-collagen 1 domains of type IV collagen [alpha(IV)NC1] were employed to exam avidity of anti-GBM antibodies using antigen-inhibition enzyme-linked immunosorbent assay. The amount of alpha(IV)NC1 needed for 50% inhibition of antibody binding was compared among patients with different clinical and pathological parameters. After the sera were diluted to give equivalent concentration of anti-GBM antibodies, the amount of alpha(IV)NC1 used for 50% inhibition was prominently different among patients, from 0.02 microg to 20 microg, with an average at 0.666 microg. A significant correlation was observed between the amount of alpha(IV)NC1 used and the percentage of glomeruli which had crescents (P=0.001). Higher avidity of anti-GBM antibodies predicted higher percentage of glomerular crescents (R2=0.58, P<0.001). No obvious change of avidity was observed in the serial samples. The results suggested that affinity maturation might have been completed by the time that patients presented with anti-GBM disease. The avidity of anti-GBM antibodies was associated with the degree of renal damage and might play a key role in the pathogenesis of anti-GBM disease.
抗肾小球基底膜（GBM）抗体介导的疾病的特征是自身抗体与GBM结合，导致快速进展性肾小球肾炎，常导致肾功能不可逆转的丧失。抗GBM抗体的肾毒性潜力已在动物实验中得到证实。我们质疑高亲和力是否会导致抗GBM抗体持续沉积，从而使炎症和肾损伤持续存在。为了验证这一假设，收集了32例患者的血清和11例抗GBM病患者的系列样本。使用抗原抑制酶联免疫吸附试验，采用纯化的IV型胶原牛α链非胶原1结构域[α(IV)NC1]检测抗GBM抗体的亲和力。比较了不同临床和病理参数患者中50%抑制抗体结合所需的α(IV)NC1量。将血清稀释至抗GBM抗体浓度相等后，不同患者用于50%抑制的α(IV)NC1量差异显著，从0.02μg到20μg不等，平均为0.666μg。观察到所用α(IV)NC1量与有新月体的肾小球百分比之间存在显著相关性（P=0.001）。抗GBM抗体的高亲和力预示着肾小球新月体百分比更高（R2=0.58，P<0.001）。系列样本中未观察到亲和力的明显变化。结果表明，在抗GBM病患者出现时，亲和力成熟可能已经完成。抗GBM抗体的亲和力与肾损伤程度相关，可能在抗GBM病的发病机制中起关键作用。
