膜性肾病的分子发病机制。

IF 28.4 1区医学 Q1 PATHOLOGY

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2020-01-24 DOI:10.1146/annurev-pathol-020117-043811

P. Ronco, H. Debiec

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引用次数: 56

摘要

膜性肾病是肾小球的一种非炎症性自身免疫性疾病，其特点是免疫沉积物的形成、补体介导的蛋白尿和肾功能衰竭的风险。随着从新生儿期到成年期病例中几个抗原[中性内肽酶、磷脂酶A2受体(PLA2R)、含血栓反应蛋白结构域7A (THSD7A)]的鉴定和抗体结合结构域(即表位)的表征，对分子发病机制的理解取得了相当大的进展。针对PLA2R的免疫接种发生在70%至80%的成人病例中。循环抗体的高度特异性和敏感性分析的发展已经引起了诊断和治疗监测的范式转变。此外，HLA- dq、HLA- dr和PLA2R1中的几个相互作用位点以及经典的人类白细胞抗原(HLA)D等位基因已被确定为危险因素，这取决于患者的种族。此外，抗体致病性的机制和补体活化的途径现在被更好地理解。进一步的研究是设计新的治疗策略的必要条件，包括确定触发事件，缓解和进展的分子基础，以及所涉及的t细胞表位。《病理学年度评论:疾病机制》第15卷预计最终在线出版日期为2020年1月24日。修订后的估计数请参阅http://www.annualreviews.org/page/journal/pubdates。

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Molecular Pathogenesis of Membranous Nephropathy.

Membranous nephropathy is a noninflammatory autoimmune disease of the kidney glomerulus, characterized by the formation of immune deposits, complement-mediated proteinuria, and risk of renal failure. Considerable advances in understanding the molecular pathogenesis have occurred with the identification of several antigens [neutral endopeptidase, phospholipase A2 receptor (PLA2R), thrombospondin domain-containing 7A (THSD7A)] in cases arising from the neonatal period to adulthood and the characterization of antibody-binding domains (that is, epitopes). Immunization against PLA2R occurs in 70% to 80% of adult cases. The development of highly specific and sensitive assays of circulating antibodies has induced a paradigm shift in diagnosis and treatment monitoring. In addition, several interacting loci in HLA-DQ, HLA-DR, and PLA2R1, as well as classical human leukocyte antigen (HLA)D alleles have been identified as being risk factors, depending on a patient's ethnicity. Additionally, mechanisms of antibody pathogenicity and pathways of complement activation are now better understood. Further research is mandatory for designing new therapeutic strategies, including the identifying triggering events, the molecular bases of remission and progression, and the Tcell epitopes involved. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 15 is January 24, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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来源期刊

Annual Review of Pathology-Mechanisms of Disease 医学-病理学

CiteScore

62.60

自引率

0.00%

发文量

期刊介绍： The Annual Review of Pathology: Mechanisms of Disease is a scholarly journal that has been published since 2006. Its primary focus is to provide a comprehensive overview of recent advancements in our knowledge of the causes and development of significant human diseases. The journal places particular emphasis on exploring the current and evolving concepts of disease pathogenesis, as well as the molecular genetic and morphological changes associated with various diseases. Additionally, the journal addresses the clinical significance of these findings. In order to increase accessibility and promote the broad dissemination of research, the current volume of the journal has transitioned from a gated subscription model to an open access format. This change has been made possible through the Annual Reviews' Subscribe to Open program, which allows all articles published in this volume to be freely accessible to readers. As part of this transition, all articles in the journal are published under a Creative Commons Attribution (CC BY) license, which encourages open sharing and use of the research.