Shu Yue, Huang Jing, Jiang Lei, Zhang Yi-Miao, Wang Fang, Wang Xin, Meng Li-Qiang, Cheng Xu-Yang, Liu Gang, Wang Su-Xia, Zhao Ming-Hui, Ronco Pierre, Cui Zhao
Renal Division, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China.
Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, Beijing, China.
Kidney Int. 2025 Mar 25. doi: 10.1016/j.kint.2025.02.028.
Anti-nephrin autoantibodies have been discovered in patients with minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS), especially in those with active nephrotic syndrome. Here, we investigated the prevalence and clinical significance of anti-nephrin antibodies in 596 adult Chinese patients (436 with MCD and 160 with primary FSGS) diagnosed by kidney biopsy. Anti-nephrin IgG and IgM were detected using ELISA, with validation through antigen-inhibition ELISA and Western blotting. Clinical data at biopsy and during the follow-up period were analyzed. Anti-nephrin antibodies were detected in 43% of all patients, with 30% testing positive for anti-nephrin IgG, 26% for anti-nephrin IgM, and 13.1% for both antibodies. The prevalence of anti-nephrin antibodies was higher in patients with nephrotic-range proteinuria who were not receiving steroids or immunosuppressants (51.1%). Patients with positive anti-nephrin antibodies exhibited more severe nephrotic syndrome, higher rates of relapse, and a shorter relapse-free period compared to those negative for these antibodies. Clinical features were similar between those with IgG and IgM. Notably, patients with both anti-nephrin IgG and IgM had the most severe proteinuria and the highest relapse frequency, suggesting a dose-dependent effect. Longitudinal analysis revealed that anti-nephrin antibodies significantly decreased during clinical remission, while they reappeared preceding proteinuria relapse. Our study shows that anti-nephrin antibodies, including IgG and IgM, are detectable in adult patients with MCD and primary FSGS and are associated with active nephrotic syndrome and frequent relapse. These antibodies may serve as valuable biomarkers and potential therapeutic targets.
在微小病变病（MCD）和原发性局灶节段性肾小球硬化症（FSGS）患者中发现了抗肾足蛋白自身抗体，尤其是在那些患有活动性肾病综合征的患者中。在此，我们调查了596例经肾活检确诊的成年中国患者（436例MCD患者和160例原发性FSGS患者）中抗肾足蛋白抗体的患病率及其临床意义。使用酶联免疫吸附测定（ELISA）检测抗肾足蛋白IgG和IgM，并通过抗原抑制ELISA和蛋白质印迹法进行验证。分析了活检时及随访期间的临床数据。在所有患者中，43%检测到抗肾足蛋白抗体，其中30%抗肾足蛋白IgG检测呈阳性，26%抗肾足蛋白IgM检测呈阳性，13.1%两种抗体均呈阳性。在未接受类固醇或免疫抑制剂治疗的肾病范围蛋白尿患者中，抗肾足蛋白抗体的患病率更高（51.1%）。与抗肾足蛋白抗体阴性的患者相比，抗肾足蛋白抗体阳性的患者表现出更严重的肾病综合征、更高的复发率和更短的无复发期。IgG和IgM阳性患者的临床特征相似。值得注意的是，抗肾足蛋白IgG和IgM均阳性的患者蛋白尿最严重，复发频率最高，提示存在剂量依赖性效应。纵向分析显示，抗肾足蛋白抗体在临床缓解期显著下降，而在蛋白尿复发前再次出现。我们的研究表明，在成年MCD和原发性FSGS患者中可检测到包括IgG和IgM在内的抗肾足蛋白抗体，这些抗体与活动性肾病综合征和频繁复发相关。这些抗体可能是有价值的生物标志物和潜在的治疗靶点。
