Is There a Diagnostic and Prognostic Role for Anti-Nephrin Autoantibodies in Diabetic Nephropathy?

IF 3 Q3 IMMUNOLOGY

Antibodies Pub Date : 2025-03-12 DOI:10.3390/antib14010025

Han Sean Lee, Henry H L Wu, Arvind Ponnusamy, Helen Alderson, Rajkumar Chinnadurai

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Abstract

Diabetic nephropathy (DN) is one of the key causes of end-stage kidney disease worldwide, especially in developed countries. The classic pathogenic development of DN is characterized by microalbuminuria which would progress to nephrotic-range proteinuria and loss of kidney function. The degree of albuminuria is considered an independent risk factor for all-cause mortality in patients with DN. It is now well established that albuminuria stems from disruptions in podocyte structure and function. Podocytes play a major role in the glomerular filtration barrier. The nephrin protein has been identified as a core component of the slit diaphragm in podocytes, and as such, the downregulation of nephrin expression has been described well in various proteinuric glomerulopathies, including DN. Previous studies have shown that the presence of urinary nephrin potentially signifies an early marker of podocyte injury in DN. More recently, there have been increasing bodies of evidence which suggest that circulating autoantibodies targeting nephrin contributes to the pathogenesis of podocytopathies. However, the functional significance of these circulating autoantibodies in patients with DN is not well understood. In this review, we aim to evaluate the significance of nephrin dysregulation in the pathogenesis of DN based on the current available literature and provide an overview on the application of circulating anti-nephrin autoantibodies in relation to its diagnostic as well as prognostic role in podocytopathies, including DN.

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抗肾素自身抗体在糖尿病肾病中的诊断和预后作用？

糖尿病肾病（DN）是世界范围内终末期肾脏疾病的主要病因之一，尤其是在发达国家。DN的典型病原发展特点是微量白蛋白尿，继而发展为肾范围蛋白尿和肾功能丧失。蛋白尿程度被认为是DN患者全因死亡率的独立危险因素。现在已经确定，蛋白尿源于足细胞结构和功能的破坏。足细胞在肾小球滤过屏障中起主要作用。nephrin蛋白已被确定为足细胞缝隙隔膜的核心成分，因此，在包括DN在内的各种蛋白尿肾小球疾病中，nephrin表达的下调已被很好地描述。先前的研究表明，尿肾素的存在可能是DN足细胞损伤的早期标志。最近，有越来越多的证据表明，循环自身抗体靶向肾素有助于足细胞病变的发病机制。然而，这些循环自身抗体在DN患者中的功能意义尚不清楚。在这篇综述中，我们的目的是在现有文献的基础上评估肾素失调在DN发病机制中的意义，并概述循环抗肾素自身抗体在包括DN在内的足细胞病变的诊断和预后中的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antibodies IMMUNOLOGY-

CiteScore

7.10

自引率

6.40%

发文量

审稿时长

11 weeks

期刊介绍： Antibodies (ISSN 2073-4468), an international, peer-reviewed open access journal which provides an advanced forum for studies related to antibodies and antigens. It publishes reviews, research articles, communications and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided. Electronic files or software regarding the full details of the calculation and experimental procedure - if unable to be published in a normal way - can be deposited as supplementary material. This journal covers all topics related to antibodies and antigens, topics of interest include (but are not limited to): antibody-producing cells (including B cells), antibody structure and function, antibody-antigen interactions, Fc receptors, antibody manufacturing antibody engineering, antibody therapy, immunoassays, antibody diagnosis, tissue antigens, exogenous antigens, endogenous antigens, autoantigens, monoclonal antibodies, natural antibodies, humoral immune responses, immunoregulatory molecules.