Provatopoulou Simella, Kalavrizioti Dimitra, Stangou Maria, Kouri Maria-Nikoleta, Kalliakmani Pantellitsa, Papasotiriou Marios, Papachristou Evangelos, Goumenos Dimitrios S, Papagianni Aikaterini
Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece.
Department of Nephrology, Hippokration General Hospital, Thessaloniki University School of Medicine, Thessaloniki, Greece.
Rom J Intern Med. 2019 Jun 1;57(2):141-150. doi: 10.2478/rjim-2018-0044.
Circulating autoantibodies against phospholipase A2 receptor (anti-PLA2R) are recognized as key elements in the pathogenesis of idiopathic membranous nephropathy. In current clinical practice, they are increasingly gaining attention as novel tools for diagnosis and disease monitoring. We investigated the diagnostic and prognostic utility of anti-PLA2R antibody measurements in Greek patients with biopsy-proven membranous nephropathy.
Anti-PLA2R levels were measured in serum samples from 33 patients at diagnosis using ELISA and were associated with treatment outcome. Moreover, serial anti-PLA2R measurements were performed in 15 patients under different clinical conditions and level alterations were correlated with disease activity.
Positive anti-PLA2R antibodies at diagnosis were found in 16 of 33 patients (48.5%). Anti-PLA2R levels were independently associated with the achievement of complete remission of nephrotic syndrome after immunosuppressive treatment compared to partial remission (p = 0.02, R2 = 0.265, 95%CI -0.019 to -0.0003). Higher detectable antibody levels at diagnosis were correlated with higher proteinuria levels (r = 0.813, p = 0.0001, 95%CI 0.532 to 0.933) and lower eGFR at the end of follow-up (r = -0.634, p = 0.0083, 95%CI -0.86 to -0.202). Serial antibody measurements during follow-up showed that anti-PLA2R titers were significantly reduced at the end of treatment after complete remission was achieved, remained low under sustained clinical remission, and increased during relapse.
Our findings confirm the usefulness of anti-PLA2R measurements in the diagnosis of idiopathic membranous nephropathy. Low levels of anti-PLA2R antibodies at diagnosis are predictive of complete remission of nephrotic syndrome following immunosuppressive treatment. Serial anti-PLA2R measurements correlate well with clinical status throughout the follow-up period and could be used routinely for monitoring of disease activity and treatment planning.
抗磷脂酶A2受体循环自身抗体（抗PLA2R）被认为是特发性膜性肾病发病机制中的关键因素。在当前临床实践中，它们作为诊断和疾病监测的新工具越来越受到关注。我们研究了抗PLA2R抗体检测在经活检证实为膜性肾病的希腊患者中的诊断和预后效用。
使用酶联免疫吸附测定法（ELISA）测量了33例患者诊断时血清样本中的抗PLA2R水平，并将其与治疗结果相关联。此外，对15例处于不同临床状况的患者进行了抗PLA2R的系列检测，其水平变化与疾病活动相关。
33例患者中有16例（48.5%）在诊断时抗PLA2R抗体呈阳性。与部分缓解相比，抗PLA2R水平与免疫抑制治疗后肾病综合征完全缓解的实现独立相关（p = 0.02，R2 = 0.265，95%置信区间-0.019至-0.0003）。诊断时可检测到的抗体水平越高，与蛋白尿水平越高相关（r = 0.813，p = 0.0001，95%置信区间0.532至0.933），且随访结束时估算肾小球滤过率（eGFR）越低（r = -0.634，p = 0.0083，95%置信区间-0.86至-0.202）。随访期间的系列抗体检测表明，在实现完全缓解后治疗结束时抗PLA2R滴度显著降低，在持续临床缓解期保持较低水平，并在复发时升高。
我们的研究结果证实了抗PLA2R检测在特发性膜性肾病诊断中的有用性。诊断时抗PLA2R抗体水平低可预测免疫抑制治疗后肾病综合征的完全缓解。抗PLA2R的系列检测在整个随访期间与临床状况相关性良好，可常规用于监测疾病活动和制定治疗计划。
