Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
Renal Research Labs, Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom.
Kidney Int. 2017 Mar;91(3):566-574. doi: 10.1016/j.kint.2016.09.048. Epub 2017 Jan 5.
Idiopathic membranous nephropathy (INM) remains a common cause of the nephrotic syndrome in adults. The autoimmune nature of IMN was clearly delineated in 2009 with the identification of the glomerular-deposited IgG to be a podocyte receptor, phospholipase A2 receptor (PLA2R) in 70% to 75% of cases. This anti-PLA2R autoantibody, predominantly the IgG4 subclass, has been quantitated in serum using an enzyme-linked immunosorbent assay and has been used to aid diagnosis and monitor response to immunosuppressive therapy. In 2014, a second autoantigen, thrombospondin type 1 domain-containing 7A (THSD7A), was identified. Immunostaining of biopsy specimens has further detected either PLA2R or THSD7A antigen in the deposited immune complexes in 5% to 10% of cases autoantibody seronegative at the time of biopsy. Therefore, the term IMN should now be superseded by the term primary or autoimmune MN (AMN) (anti-PLA2R or anti-THSD7A positive) classifying ∼80% to 90% of cases previously designated IMN. Cases of secondary MN associated with other diseases show much lower association with these autoantibodies, but their true incidence in secondary cases still needs to be defined. How knowledge of the autoimmune mechanism and the sequential measurement of these autoantibodies is likely to change the clinical management and trajectory of AMN by more precisely defining its diagnosis, prognosis, and treatment is discussed. Their application early in the disease course to new and old therapies will provide additional precision to AMN management. We also review innovative therapeutic approaches on the horizon that are expected to lead to our ultimate goal of improved patient care in A(I)MN.
特发性膜性肾病（IMN）仍然是成人肾病综合征的常见病因。2009 年，随着识别出肾小球沉积的 IgG 是足细胞受体，即磷脂酶 A2 受体（PLA2R），IMN 的自身免疫性质得到了明确的描述，在 70%至 75%的病例中。这种抗 PLA2R 自身抗体，主要是 IgG4 亚类，已使用酶联免疫吸附测定法在血清中定量，并已用于辅助诊断和监测免疫抑制治疗的反应。2014 年，第二种自身抗原，血小板反应蛋白 1 型结构域包含 7A（THSD7A）被鉴定出来。免疫组化染色进一步检测到活检标本中沉积的免疫复合物中存在 PLA2R 或 THSD7A 抗原，在活检时该自身抗体呈阴性的病例占 5%至 10%。因此，现在应该用原发性或自身免疫性 MN（AMN）（抗 PLA2R 或抗 THSD7A 阳性）一词来替代 IMN 一词，将以前命名为 IMN 的约 80%至 90%的病例进行分类。与其他疾病相关的继发性 MN 与这些自身抗体的关联度要低得多，但它们在继发性病例中的真实发生率仍需确定。讨论了对自身免疫机制的认识和对这些自身抗体的连续测量如何通过更精确地定义其诊断、预后和治疗来改变 AMN 的临床管理和病程。在疾病早期应用这些自身抗体对新老治疗方法将为 AMN 管理提供额外的准确性。我们还回顾了预期会导致改善 A(I)MN 患者护理的创新治疗方法。
