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原发性足细胞病患者中突触素和膜联蛋白1抗体水平升高。

Increased levels of antibodies to synaptopodin and annexin 1 in patients with primary podocytopathies.

作者信息

Chebotareva Natalia V, Charionovskaya Evgeniya A, Biryukova Evgenia A, Vinogradov Anatoliy A, Alentov Igor I, Sergeeva Natalia S, Kononikhin Alexey S, Nikolaev Evgeny N, Moiseev Sergey V

机构信息

Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia.

Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russia.

出版信息

Front Nephrol. 2024 Oct 31;4:1471078. doi: 10.3389/fneph.2024.1471078. eCollection 2024.

DOI:10.3389/fneph.2024.1471078
PMID:39544697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11560892/
Abstract

INTRODUCTION

Circulating anti-podocyte antibodies have been proposed as potential factors contributing to increased permeability in primary podocytopathies, such as Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS). The aim of the study was to to assess the levels of antibodies targeting synaptopodin and annexin 1 in the blood serum of patients diagnosed with nephrotic syndrome, with the aim of evaluating their potential utility in diagnosing primary podocytopathies and predicting therapeutic response.

METHODS

The study included a total of 72 patients diagnosed with nephrotic syndrome, alongside 21 healthy subjects for comparison. Among the patients, 38 were diagnosed with FSGS, 12 with MCD, and 22 with MN. The levels of anti-synaptopodin and anti-annexin-1 antibodies were quantified using Enzyme-Linked Immunosorbent Assay.

RESULTS

The levels of antibodies to annexin 1 and anti-synaptopodin in the blood were found to be higher in patients diagnosed with MCD and FSGS compared to those with MN and healthy individuals. The elevated levels of antibodies to annexin 1 and synaptopodin showed area under the curve values of 0.826 (95% CI 0.732-0.923) and 0.827 (95% CI 0.741-0.879), respectively. However, a model incorporating both antibodies demonstrated higher sensitivity (80.9%) and specificity (81.3%) with an AUC of 0.859 (95% CI 0.760-0.957). Notably, serum levels of annexin 1 and anti-synaptopodin antibodies did not predict the response to prednisolone and/or CNI therapy.

DISCUSSION

Levels of antibodies targeting synaptopodin and annexin 1 were notably elevated in patients diagnosed with MCD and FSGS compared to those with MN and healthy controls. A panel comprising both antibodies demonstrated moderate to high sensitivity and specificity for diagnosis MCD or FSGS.

摘要

引言

循环抗足细胞抗体被认为是导致原发性足细胞病(如微小病变病(MCD)和局灶节段性肾小球硬化(FSGS))通透性增加的潜在因素。本研究的目的是评估诊断为肾病综合征的患者血清中靶向突触素和膜联蛋白1的抗体水平,以评估其在诊断原发性足细胞病和预测治疗反应方面的潜在效用。

方法

本研究共纳入72例诊断为肾病综合征的患者,同时纳入21名健康受试者作为对照。患者中,38例诊断为FSGS,12例诊断为MCD,22例诊断为MN。采用酶联免疫吸附测定法对血清中抗突触素和抗膜联蛋白1抗体水平进行定量。

结果

与MN患者和健康个体相比,诊断为MCD和FSGS的患者血液中膜联蛋白1抗体和抗突触素抗体水平更高。膜联蛋白1抗体和突触素抗体水平升高时,曲线下面积值分别为0.826(95%CI 0.732-0.923)和0.827(95%CI 0.741-0.879)。然而,同时包含这两种抗体的模型显示出更高的敏感性(80.9%)和特异性(81.3%),AUC为0.859(95%CI 0.760-0.957)。值得注意的是,膜联蛋白1和抗突触素抗体的血清水平不能预测对泼尼松龙和/或钙调神经磷酸酶抑制剂治疗的反应。

讨论

与MN患者和健康对照相比,诊断为MCD和FSGS的患者中靶向突触素和膜联蛋白1的抗体水平显著升高。包含这两种抗体的检测组合对MCD或FSGS的诊断显示出中度至高敏感性和特异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7a/11560892/a3948e951f40/fneph-04-1471078-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7a/11560892/a2ad8d2c28ae/fneph-04-1471078-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7a/11560892/8443def00b7b/fneph-04-1471078-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7a/11560892/a3948e951f40/fneph-04-1471078-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7a/11560892/a2ad8d2c28ae/fneph-04-1471078-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7a/11560892/8443def00b7b/fneph-04-1471078-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7a/11560892/a3948e951f40/fneph-04-1471078-g003.jpg

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A pilot study of anti-nephrin antibodies in podocytopaties among adults.成人足细胞病中抗肾足突蛋白抗体的一项初步研究。
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Current understanding of the molecular mechanisms of circulating permeability factor in focal segmental glomerulosclerosis.
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Front Med (Lausanne). 2023 Jun 20;10:1189017. doi: 10.3389/fmed.2023.1189017. eCollection 2023.
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Circulating Permeability Factors in Focal Segmental Glomerulosclerosis:   Detection.局灶节段性肾小球硬化症中的循环通透性因子:检测
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