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期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2314471

摘要内容如下：

背景

成人的微小病变和原发性局灶节段性肾小球硬化，以及儿童的特发性肾病综合征，是免疫介导的足细胞病变，导致肾病综合征。靶向nephrin的自身抗体已在微小病变患者中发现，但其临床和病理生理作用尚不清楚。

方法

我们进行了一项多中心研究，以分析患有肾小球疾病（包括微小病变肾病、局灶节段性肾小球硬化、膜性肾病、IgA肾病、抗中性粒细胞胞浆抗体相关性肾小球肾炎和狼疮性肾炎）的成人以及患有特发性肾病综合征的儿童和对照组中的抗肾素自身抗体。我们还通过重组鼠nephrin的主动免疫建立了实验小鼠模型。

结果

该研究包括539名患者（357名成人和182名儿童）和117名对照。在成人中，105例微小病变患者中有46例（44%）、74例原发性局灶节段性肾小球硬化患者中有7例（9%）发现了抗肾上腺素自身抗体，而在其他疾病患者中仅有极少数病例发现了抗肾上腺素自身抗体。在182名患有特发性肾病综合征的儿童中，94名（52%）可检测到抗肾上腺素自身抗体。在未接受免疫抑制治疗的活动性微小病变或特发性肾病综合征患者亚组中，抗肾素自身抗体的患病率分别高达69%和90%。在研究纳入时和随访期间，抗肾上腺素自身抗体水平与疾病活动相关。在小鼠中，实验性免疫诱导了肾病综合征、微小改变疾病样表型、IgG定位于足细胞裂孔隔膜、nephrin磷酸化和严重的细胞骨架改变。

结论

在这项研究中，循环中的抗肾上腺素自身抗体在微小病变肾病或特发性肾病综合征患者中很常见，似乎是疾病活动的标志。它们在裂孔隔膜处的结合导致足细胞功能障碍和肾病综合征，这突出了它们的病理生理学意义。（由德国研究基金会和其他机构资助）。

英文原文如下：

Abstracts

BACKGROUND  Minimal change disease and primary focal segmental glomerulosclerosis in adults, along with idiopathic nephrotic syndrome in children, are immune-mediated podocytopathies that lead to nephrotic syndrome. Autoantibodies targeting nephrin have been found in patients with minimal change disease, but their clinical and pathophysiological roles are unclear.

METHODS  We conducted a multicenter study to analyze antinephrin autoantibodies in adults with glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, antineutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis, as well as in children with idiopathic nephrotic syndrome and in controls. We also created an experimental mouse model through active immunization with recombinant murine nephrin.

RESULTS  The study included 539 patients (357 adults and 182 children) and 117 controls. Among the adults, antinephrin autoantibodies were found in 46 of the 105 patients (44%) with minimal change disease, 7 of 74 (9%) with primary focal segmental glomerulosclerosis, and only in rare cases among the patients with other conditions. Of the 182 children with idiopathic nephrotic syndrome, 94 (52%) had detectable antinephrin autoantibodies. In the subgroup of patients with active minimal change disease or idiopathic nephrotic syndrome who were not receiving immunosuppressive treatment, the prevalence of antinephrin autoantibodies was as high as 69% and 90%, respectively. At study inclusion and during follow-up, antinephrin autoantibody levels were correlated with disease activity. Experimental immunization induced a nephrotic syndrome, a minimal change disease-like phenotype, IgG localization to the podocyte slit diaphragm, nephrin phosphorylation, and severe cytoskeletal changes in mice.

CONCLUSIONS  In this study, circulating antinephrin autoantibodies were common in patients with minimal change disease or idiopathic nephrotic syndrome and appeared to be markers of disease activity. Their binding at the slit diaphragm induced podocyte dysfunction and nephrotic syndrome, which highlights their pathophysiological significance. (Funded by Deutsche Forschungsgemeinschaft and others.).

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