PLA2R-IgG4 抗体作为特发性膜性肾病患者治疗效果和预后评估的预测生物标志物：一项回顾性研究。
PLA2R-IgG4 antibody as a predictive biomarker of treatment effectiveness and prognostic evaluation in patients with idiopathic membranous nephropathy: a retrospective study.
机构信息
Department of Nephrology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.
出版信息
PeerJ. 2022 Oct 10;10:e14193. doi: 10.7717/peerj.14193. eCollection 2022.
BACKGROUND
The Kidney Disease Improving Global Outcomes (KDIGO) 2021 guidelines recommend Rituximab (RTX) as the first-line therapy and phospholipase A2 receptor (PLA2R) antibody as a biomarker for remission and prognosis in patients with idiopathic membranous nephropathy (IMN).
METHODS
This study was a retrospective analysis of 70 patients with IMN treated with either rituximab (RTX) or cyclophosphamide (CTX) and steroid. Quantitative detection of PLA2R-IgG and PLA2R-IgG4 antibodies at sixth month after treatment, determined using time-resolved fluoroimmunoassay (TRFIA), were used for treatment effectiveness analysis and prognostic evaluation in patients with IMN.
RESULTS
After 12 months of therapy, the remission rate of proteinuria, including complete remission (CR) and partial remission (PR) in the RTX group and the CTX group, were 74% versus 67.5% ( = 0.114), respectively. Both PLA2R-IgG and PLA2R-IgG4 levels were decreased in patients with remission of proteinuria after 6 months of therapy. Receiver operating characteristic curve (ROC) curve analysis exhibited that the AUC of PLA2R-IgG4 and the PLA2R-IgG as laboratory criteria for proteinuria remission were 0.970 versus 0.886 ( = 0.0516), respectively, after 6 months of treatment. The cut-off value of PLA2R-IgG4 was 7.67 RU/mL and the sensitivity and specificity of remission rate at 6th month were 90.9% and 100%, respectively. Furthermore, the AUC of the PLA2R-IgG4 and PLA2R-IgG to predict the outcome after 12 months of treatment were 0.922 versus 0.897 ( = 0.3270), respectively. With the cut-off value of PLA2R-IgG4 being 22.985 RU/mL, the sensitivity and specificity of remission rate at 12th month were 100% and 87.1%, respectively. Logistic regression analysis revealed that the PLA2R-IgG4 level ( = 0.023), the rate of decrease of PLA2R-IgG4 level ( = 0.034), and eGFR level ( = 0.012) were significantly associated with remission.
CONCLUSIONS
We found that the patients in the RTX group and CTX group achieved effective remission of proteinuria after 12 months of treatment. PLA2R-IgG4 may be a more effective biomarker for treatment effectiveness analysis and prognostic assessment, compared with anti-PLA2R-IgG for PLA2R associated IMN.
背景
肾脏疾病改善全球结果（KDIGO）2021 指南建议利妥昔单抗（RTX）作为特发性膜性肾病（IMN）患者的一线治疗药物，磷脂酶 A2 受体（PLA2R）抗体作为缓解和预后的生物标志物。
方法
本研究是对 70 例接受利妥昔单抗（RTX）或环磷酰胺（CTX）联合激素治疗的 IMN 患者进行的回顾性分析。采用时间分辨荧光免疫分析法（TRFIA）定量检测治疗后第 6 个月的 PLA2R-IgG 和 PLA2R-IgG4 抗体，用于分析 IMN 患者的治疗效果和预后评估。
结果
治疗 12 个月后，RTX 组和 CTX 组蛋白尿完全缓解（CR）和部分缓解（PR）的缓解率分别为 74%和 67.5%（=0.114）。治疗 6 个月后，蛋白尿缓解患者的 PLA2R-IgG 和 PLA2R-IgG4 水平均降低。接受者操作特征曲线（ROC）曲线分析显示，治疗 6 个月后，PLA2R-IgG4 和 PLA2R-IgG 作为蛋白尿缓解的实验室标准，其 AUC 分别为 0.970 和 0.886（=0.0516）。PLA2R-IgG4 的截断值为 7.67 RU/mL，6 个月时的缓解率为 90.9%和 100%，灵敏度和特异性分别为 90.9%和 100%。此外，PLA2R-IgG4 和 PLA2R-IgG 预测治疗 12 个月后结局的 AUC 分别为 0.922 和 0.897（=0.3270）。PLA2R-IgG4 的截断值为 22.985 RU/mL，12 个月时的缓解率为 100%和 87.1%，灵敏度和特异性分别为 100%和 87.1%。Logistic 回归分析显示，PLA2R-IgG4 水平（=0.023）、PLA2R-IgG4 水平下降率（=0.034）和 eGFR 水平（=0.012）与缓解显著相关。
结论
我们发现 RTX 组和 CTX 组患者在治疗 12 个月后均实现了蛋白尿的有效缓解。与抗 PLA2R-IgG 相比，PLA2R-IgG4 可能是一种更有效的治疗效果分析和预后评估的生物标志物，用于 PLA2R 相关的 IMN。
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