Microbiology and Virology Department, S. Carlo Borromeo Hospital, Milano, Italy.
Clinical Immunology & Renal Unit, S. Carlo Borromeo Hospital, Milano, Italy; Renal Unit, S. Carlo Borromeo Hospital, Milano, Italy.
Autoimmun Rev. 2016 Feb;15(2):146-54. doi: 10.1016/j.autrev.2015.10.004. Epub 2015 Oct 23.
Autoantibodies to M-type phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (IMN). They can differentiate IMN from other glomerular diseases and primary from secondary forms of MN. Preliminary data suggest that anti-PLA2R antibody titer correlates with disease activity but more solid evidence is needed. To evaluate the performance of anti-PLA2R antibody for monitoring nephropathy activity, 149 anti-PLA2R antibody measurements were performed during the follow-up of 42 biopsy proven IMN consecutive patients. Patients were enrolled either at time of diagnosis (33 cases, inception cohort) or after diagnosis (9 patients, non-inception cohort). Anti-PLA2R detection was performed using the highly sensitive transfected cell-based indirect immunofluorescence (IIFT). Over the follow-up there was a linear time-trend of decreasing proteinuria (P<0.001), increasing serum albumin (P<0.001) and decreasing PLA2R antibody levels (P=0.002). There was a statistically significant association between changes in PLA2R antibody levels and the clinical course of PLA2R-positive IMN. The positive PLA2R serum antibody status was linearly associated with increasing proteinuria and decreasing serum albumin over time, compared with negative antibody status. Moreover, the strong correlation between the clinical conditions and PLA2R antibody levels allowed the prediction of prevalence distribution of patients with active disease, partial and complete remission. Over the course of the follow-up, the probability of halving proteinuria increased 6.5 times after disappearance of PLA2R antibodies. Our data suggest that the serial evaluation of anti-PLA2R antibodies could help in optimal timing and duration of the immunosuppressive therapy, reducing over(under)-treatment and associated side-effects.
抗 M 型磷脂酶 A2 受体（PLA2R）自身抗体是特发性膜性肾病（IMN）的特异性标志物。它们可以将 IMN 与其他肾小球疾病以及原发性和继发性 MN 区分开来。初步数据表明，抗 PLA2R 抗体滴度与疾病活动度相关，但需要更多确凿的证据。为了评估抗 PLA2R 抗体监测肾病活动的性能，对 42 例经活检证实的 IMN 连续患者的随访中进行了 149 次抗 PLA2R 抗体测量。患者要么在诊断时（33 例，起始队列），要么在诊断后（9 例，非起始队列）入组。使用高度敏感的转染细胞基于间接免疫荧光（IIFT）进行抗 PLA2R 检测。在随访过程中，蛋白尿呈线性下降趋势（P<0.001），血清白蛋白增加（P<0.001），PLA2R 抗体水平下降（P=0.002）。PLA2R 阳性 IMN 的临床病程与 PLA2R 抗体水平的变化之间存在统计学显著关联。与抗体阴性状态相比，PLA2R 血清抗体阳性状态与蛋白尿的增加和血清白蛋白的减少呈线性相关。此外，临床状况和 PLA2R 抗体水平之间的强相关性允许预测活动性疾病、部分缓解和完全缓解患者的患病率分布。在随访过程中，PLA2R 抗体消失后，蛋白尿减半的概率增加了 6.5 倍。我们的数据表明，连续评估抗 PLA2R 抗体可能有助于确定免疫抑制治疗的最佳时机和持续时间，减少过度（不足）治疗和相关副作用。
