Podocytopathies represent a group of glomerular disorders associated with minimal changes (MC) or focal segmental glomerulosclerosis (FSGS) lesion patterns at biopsy and heterogeneous responses to steroids. Anti-nephrin antibodies were previously found in such patients, suggesting an autoimmune form of podocytopathy. High resolution confocal microscopy on kidney biopsies of a cohort of 128 pediatric patients revealed localization of IgG along the slit diaphragm in 30% of patients with MC and 25% of those with FSGS, but not in other lesion patterns. Anti-nephrin IgG ELISA assay in the serum and stimulated emission depletion microscopy of kidney biopsies showed IgG-nephrin co-localization only in 77.8% of cases. Similar observations were obtained in a cohort of 48 adult patients with MC or FSGS at kidney biopsy, where IgG-nephrin colocalization was only 44.4%, suggesting the existence of autoantibodies binding to other slit proteins. Patients with anti-slit antibodies showed nephrotic syndrome at onset in 94.4% of cases. Patients with primary steroid-resistance had anti-slit antibodies in 27%, while those with secondary steroid-resistance in 87.5% of cases, irrespective of the histopathological lesion pattern. Steroid-resistant patients with anti-slit antibodies responded to second-line immunosuppressants in 92.3% vs. only 20% of patients that were anti-slit negative. No patient with anti-slit antibodies developed kidney failure vs. 51.7% of those negative for antibodies (66.7% with a genetic cause and 41.2% with a non-genetic cause). Thus, the detection of anti-slit antibodies can identify patients with an autoimmune podocytopathy responsive to treatment with second-line immunosuppressants, irrespective of the histopathological lesion pattern at biopsy.

中文翻译：

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肾活检显示抗裂隙膈肌抗体可识别对二线免疫抑制剂有反应的类固醇耐药肾病综合征患儿患者


足细胞病是一组与活检时微小变化 （MC） 或局灶节段性肾小球硬化 （FSGS） 病变模式和对类固醇的异质反应相关的肾小球疾病。以前在此类患者中发现了抗肾素抗体，表明足细胞病的自身免疫性形式。对一组 128 名儿科患者的肾活检进行高分辨率共聚焦显微镜检查显示，30% 的 MC 患者和 25% 的 FSGS 患者 IgG 沿裂隙隔膜定位，但在其他病变模式中没有。血清中的抗肾素 IgG ELISA 测定和肾活检的受刺激发射耗竭显微镜检查显示 IgG-肾素共定位仅在 77.8% 的病例中。在肾活检时，在 48 名成年 MC 或 FSGS 患者队列中获得了类似的观察结果，其中 IgG-肾素共定位仅为 44.4%，表明存在与其他狭缝蛋白结合的自身抗体。94.4% 的病例在发病时显示 nephoritic syndrome。原发性类固醇耐药患者有 27% 的病例具有抗裂隙抗体，而具有继发性类固醇耐药的患者有 87.5% 的病例，无论组织病理学病变模式如何。具有抗裂隙抗体的类固醇耐药患者对二线免疫抑制剂的反应为 92.3%，而抗裂隙阴性的患者只有 20%。没有抗裂隙抗体患者发生肾衰竭，而抗体阴性的患者为 51.7% （66.7% 为遗传原因，41.2% 为非遗传原因）。因此，抗裂隙抗体的检测可以识别对二线免疫抑制剂治疗有反应的自身免疫性足细胞病患者，无论活检时的组织病理学病变模式如何。