Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada.
Urological Cancer Center for Research and Innovation (UCCRI), St Joseph's Hospital, Hamilton, ON L8N 4A6, Canada.
Biomolecules. 2021 Mar 30;11(4):513. doi: 10.3390/biom11040513.
Membranous nephropathy (MN) is an autoimmune disease of the kidney glomerulus and one of the leading causes of nephrotic syndrome. The disease exhibits heterogenous outcomes with approximately 30% of cases progressing to end-stage renal disease. The clinical management of MN has steadily advanced owing to the identification of autoantibodies to the phospholipase A2 receptor (PLA2R) in 2009 and thrombospondin domain-containing 7A (THSD7A) in 2014 on the podocyte surface. Approximately 50-80% and 3-5% of primary MN (PMN) cases are associated with either anti-PLA2R or anti-THSD7A antibodies, respectively. The presence of these autoantibodies is used for MN diagnosis; antibody levels correlate with disease severity and possess significant biomarker values in monitoring disease progression and treatment response. Importantly, both autoantibodies are causative to MN. Additionally, evidence is emerging that NELL-1 is associated with 5-10% of PMN cases that are PLA2R- and THSD7A-negative, which moves us one step closer to mapping out the full spectrum of PMN antigens. Recent developments suggest exostosin 1 (EXT1), EXT2, NELL-1, and contactin 1 (CNTN1) are associated with MN. Genetic factors and other mechanisms are in place to regulate these factors and may contribute to MN pathogenesis. This review will discuss recent developments over the past 5 years.
膜性肾病（MN）是一种肾脏肾小球的自身免疫性疾病，也是肾病综合征的主要病因之一。该疾病的临床表现具有异质性，约 30%的病例会进展为终末期肾病。由于在 2009 年发现了足细胞表面的磷脂酶 A2 受体（PLA2R）和 2014 年发现了血小板反应蛋白域包含 7A（THSD7A）自身抗体，MN 的临床治疗得到了稳步推进。大约 50-80%和 3-5%的原发性 MN（PMN）病例分别与抗 PLA2R 或抗 THSD7A 抗体相关。这些自身抗体的存在用于 MN 的诊断；抗体水平与疾病严重程度相关，并在监测疾病进展和治疗反应方面具有重要的生物标志物价值。重要的是，这两种自身抗体都是导致 MN 的原因。此外，有证据表明，NELL-1 与 5-10%的 PLA2R 和 THSD7A 阴性的 PMN 病例有关，这使我们更接近绘制出完整的 PMN 抗原图谱。最近的研究进展表明，外生骨疣 1（EXT1）、EXT2、NELL-1 和接触蛋白 1（CNTN1）与 MN 有关。遗传因素和其他机制可以调节这些因素，并可能导致 MN 的发病机制。本文将讨论过去 5 年来的最新研究进展。
