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膜性肾病的观点。

Perspectives in membranous nephropathy.

机构信息

III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

Cell Tissue Res. 2021 Aug;385(2):405-422. doi: 10.1007/s00441-021-03429-4. Epub 2021 Apr 6.

DOI:10.1007/s00441-021-03429-4
PMID:33825066
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8523383/
Abstract

The identification of the phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain-containing protein 7A (THSD7A) as podocyte antigens in adult patients with membranous nephropathy (MN) has strongly impacted both experimental and clinical research on this disease. Evidence has been furnished that podocyte-directed autoantibodies can cause MN, and novel PLA2R- and THSD7A-specific animal models have been developed. Today, measurement of serum autoantibody levels and staining of kidney biopsies for the target antigens guides MN diagnosis and treatment worldwide. Additionally, anti-PLA2R antibodies have been proven to be valuable prognostic biomarkers in MN. Despite these impressive advances, a variety of questions regarding the disease pathomechanisms, clinical use of antibody measurement, and future treatments remain unanswered. In this review, we will outline recent advances made in the field of MN and discuss open questions and perspectives with a focus on novel antigen identification, mechanisms of podocyte injury, clinical use of antibody measurement to guide diagnosis and treatment, and the potential of innovative, pathogenesis-based treatment strategies.

摘要

磷脂酶 A2 受体 1（PLA2R）和血小板反应蛋白 1 型域包含蛋白 7A（THSD7A）在成人膜性肾病（MN）患者中的足细胞抗原的鉴定，强烈影响了该疾病的实验和临床研究。有证据表明，足细胞靶向自身抗体可引起 MN，并且已经开发出新型 PLA2R 和 THSD7A 特异性动物模型。如今，血清自身抗体水平的测量和肾脏活检中靶抗原的染色指导着全球 MN 的诊断和治疗。此外，抗 PLA2R 抗体已被证明是 MN 有价值的预后生物标志物。尽管取得了这些令人印象深刻的进展，但关于疾病发病机制、抗体测量的临床应用以及未来治疗方法的各种问题仍未得到解答。在这篇综述中，我们将概述 MN 领域的最新进展，并讨论未解决的问题和前景，重点关注新抗原的鉴定、足细胞损伤的机制、抗体测量在指导诊断和治疗中的临床应用，以及基于发病机制的创新治疗策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c8/8523383/b1e0bb5d8618/441_2021_3429_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c8/8523383/11b223a03c13/441_2021_3429_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c8/8523383/82191844b6fd/441_2021_3429_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c8/8523383/1cad29d342cd/441_2021_3429_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c8/8523383/b1e0bb5d8618/441_2021_3429_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c8/8523383/11b223a03c13/441_2021_3429_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c8/8523383/82191844b6fd/441_2021_3429_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c8/8523383/1cad29d342cd/441_2021_3429_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c8/8523383/b1e0bb5d8618/441_2021_3429_Fig4_HTML.jpg

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Front Immunol. 2020 Nov 26;11:574997. doi: 10.3389/fimmu.2020.574997. eCollection 2020.
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Experimental Antiglomerular Basement Membrane GN Induced by a Peptide from .实验性抗肾小球基底膜 GN 由 肽诱导。
J Am Soc Nephrol. 2020 Jun;31(6):1282-1295. doi: 10.1681/ASN.2019060619.
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Proteomic Analysis of Complement Proteins in Membranous Nephropathy.膜性肾病中补体蛋白的蛋白质组学分析
Kidney Dis (Basel). 2023 Aug 8;9(6):507-516. doi: 10.1159/000533294. eCollection 2023 Dec.
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Causal effects of rheumatoid arthritis or ankylosing spondylitis on membranous nephropathy: a two-sample Mendelian randomization study.类风湿性关节炎或强直性脊柱炎对膜性肾病的因果效应：一项两样本孟德尔随机化研究。
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Combination of Rituximab and Low-dose Tacrolimus in the Treatment of Refractory Membranous Nephropathy: A Retrospective Cohort Study.利妥昔单抗联合低剂量他克莫司治疗难治性膜性肾病：一项回顾性队列研究。
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Non-functional ubiquitin C-terminal hydrolase L1 drives podocyte injury through impairing proteasomes in autoimmune glomerulonephritis.非功能性泛素 C 末端水解酶 L1 通过损害自身免疫性肾小球肾炎中的蛋白酶体导致足细胞损伤。
Nat Commun. 2023 Apr 13;14(1):2114. doi: 10.1038/s41467-023-37836-8.
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