抗PLA2R抗体在原发性膜性肾病诊治中的意义

The significance of anti-PLA2R antibody in the diagnosis and treatment of primary membranous nephropathy

原发性膜性肾病(primary membranous nephropathy,PMN)是一种自身免疫性疾病,其主要成因是自身抗体攻击了位于足细胞上的抗原成分,如近期发现的足细胞M型磷脂酶A2受体(M-type phospholipase A2 receptor,PLA2R)、1型血小板反应蛋白7A域(thrombospondin type-1 domain-containing 7A,THSD7A)及exostosin 1/2(EXT1/2)。目前,THSD7A以及EXT1/2抗原抗体检测在PMN中的应用尚处于新兴阶段,而抗PLA2R抗体(anti-PLA2R)的定量检测已经可以通过商业渠道获得,且anti-PLA2R是否阳性可以为临床及免疫病理鉴别原发性及继发性膜性肾病提供重要信息。anti-PLA2R水平与疾病活动密切相关。低anti-PLA2R基线水平或anti-PLA2R滴度下降预示PMN自发缓解,因此更倾向于采用保守治疗;与此相反,高anti-PLA2R基线水平或anti-PLA2R滴度升高与蛋白尿持续不缓解、肾功能进行性下降相关,因而倾向于启动免疫抑制治疗。血清anti-PLA2R水平可以预示治疗效果,治疗后的anti-PLA2R水平可预测PMN的远期预后。在疾病复发前,anti-PLA2R可重现或滴度升高,肾移植后的anti-PLA2R持续阳性或再现提示PMN复发。我们提议将这一基于血清学的检查个体化地用于诊断评估PMN,以补充完善既往的评估方法、改善PMN预后。

Primary membranous nephropathy(PMN)is a glomerulus-specific autoimmune disorder mainly caused by challenge of autoantibodies against the recently discovered antigens located on podocytes,such as the M-type phospholipase A2 receptor(PLA2R),the thrombospondin type-1 domain-containing 7A(THSD7A)and exostosin 1/2(EXT1/2).At present,the detection of anti-THSD7A and anti-EXT1/2 in PMN are still in an emerging stage,but the quantitative detection of anti-M-type phospholipase A2 receptor antibody(anti-PLA2R)is commercially available.The identification of anti-PLA2R provides important information for clinical and immunopathological differential diagnosis of primary and secondary membranous nephropathy.Anti-PLA2R levels are closely related to disease activity.Low anti-PLA2R baseline levels or decreased anti-PLA2R titers strongly predict spontaneous remission of PMN and are therefore more likely to be treated conservatively.In contrast,high anti-PLA2R baseline levels or elevated anti-PLA2R titers are associated with continuous presence of proteinuria and progressive decline in renal function,and thus tends to initiate immunosuppressive therapy.Serum anti-PLA2R levels can predict therapeutic effect,and the anti-PLA2R levels after treatment can predict long-term prognosis of PMN.Anti-PLA2R may reappear or increase before the disease relapse,and when anti-PLA2R keeps positive or reappears after kidney transplantation,it suggests relapse of PMN.We propose to use this serological-based individualized test in the diagnosis and assessment of PMN to supplement and improve the previous assessment method and increase prognosis of PMN.