抗磷脂酶A₂受体（PLA₂R）抗体与特发性膜性肾病免疫抑制治疗后结局的关联
Association of anti-PLA₂R antibodies with outcomes after immunosuppressive therapy in idiopathic membranous nephropathy.
作者信息
Bech Anneke P, Hofstra Julia M, Brenchley Paul E, Wetzels Jack F M
机构信息
Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands; and
Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands; and.
出版信息
Clin J Am Soc Nephrol. 2014 Aug 7;9(8):1386-92. doi: 10.2215/CJN.10471013. Epub 2014 Jul 17.
BACKGROUND
The optimal timing and duration of immunosuppressive therapy for idiopathic membranous nephropathy (iMN) have been debated. This study aimed to evaluate whether measuring the antibody against the phospholipase A2 receptor (PLA2R-ab) at start and end of therapy predicts long-term outcome and therefore may inform this debate.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This observational study included all consecutive high-risk patients with progressive iMN observed from 1997 to 2005 and treated with oral cyclophosphamide (CP) or mycophenolate mofetil (MMF) in combination with corticosteroids for 12 months. Patients were prospectively followed, and outcome was ascertained up to 5 years after completion of immunosuppressive therapy. Serum samples were collected before and after completion of therapy. PLA2R antibodies were determined retrospectively in stored samples using ELISA.
RESULTS
In total, 48 patients (37 men) were included. The median age was 55 years (range, 34-75), and the median serum creatinine level was 1.60 mg/dl (range, 0.98-3.37 mg/dl). Twenty-two patients received MMF and 26 received CP. At baseline, PLA2R-abs were present in 34 patients (71%). Baseline characteristics and outcome did not significantly differ between patients negative or positive for PLA2R-ab. In PLA2R-ab-positive patients, treatment resulted in a rapid decrease of antibodies: median anti-PLA2R-ab, 428 U/ml (range, 41-16,260 U/ml) at baseline and 24 U/ml (range, 0-505 U/ml) after 2 months. The PLA2R-ab levels at baseline did not predict initial response, but antibody status at end of therapy predicted long-term outcome: After 5 years, 14 of 24 (58%) antibody-negative patients were in persistent remission compared with 0 of 9 (0%) antibody-positive patients (P=0.003).
CONCLUSIONS
These data suggest that in PLA2R-ab-positive patients, measuring PLA2R-abs at the end of therapy predicts the subsequent course.
背景
特发性膜性肾病（iMN）免疫抑制治疗的最佳时机和持续时间一直存在争议。本研究旨在评估在治疗开始和结束时检测抗磷脂酶A2受体抗体（PLA2R-ab）是否能预测长期预后，从而为这一争议提供参考。
设计、地点、参与者及测量方法：这项观察性研究纳入了1997年至2005年期间观察到的所有连续的进展性iMN高危患者，这些患者接受口服环磷酰胺（CP）或霉酚酸酯（MMF）联合皮质类固醇治疗12个月。对患者进行前瞻性随访，在免疫抑制治疗完成后长达5年确定预后情况。在治疗前后收集血清样本。使用酶联免疫吸附测定法（ELISA）对储存样本中的PLA2R抗体进行回顾性检测。
结果
总共纳入了48例患者（37例男性）。中位年龄为55岁（范围34 - 75岁），中位血清肌酐水平为1.60mg/dl（范围0.98 - 3.37mg/dl）。22例患者接受MMF治疗，26例接受CP治疗。基线时，34例患者（71%）存在PLA2R-abs。PLA2R-ab阴性或阳性患者的基线特征和预后无显著差异。在PLA2R-ab阳性患者中，治疗导致抗体迅速下降：基线时抗PLA2R-ab中位值为428U/ml（范围41 - 16,260U/ml），2个月后为24U/ml（范围0 - 505U/ml）。基线时的PLA2R-ab水平不能预测初始反应，但治疗结束时的抗体状态可预测长期预后：5年后，24例抗体阴性患者中有14例（58%）持续缓解，而9例抗体阳性患者中无1例（0%）缓解（P = 0.003）。
结论
这些数据表明，在PLA2R-ab阳性患者中，治疗结束时检测PLA2R-abs可预测后续病程。
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