Prognostic value of PLA2R autoimmunity detected by measurement of anti-PLA2R antibodies combined with detection of PLA2R antigen in membranous nephropathy: A single-centre study over 14 years.
Prognostic value of PLA2R autoimmunity detected by measurement of anti-PLA2R antibodies combined with detection of PLA2R antigen in membranous nephropathy: A single-centre study over 14 years.
复制标题
DOI：
10.1371/journal.pone.0173201
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ronco P
中科院分区：
文献类型：
--
作者：
Pourcine F;Dahan K;Mihout F;Cachanado M;Brocheriou I;Debiec H;Ronco P
膜性肾病（MN）的临床过程很难预测。循环抗PLA 2 R自身抗体（PLA 2 R-Ab）的测量和PLA 2 R抗原（PLA 2 R-Ag）的免疫沉积物中的检测是疾病理解的主要进展。我们评估了这些生物标志物的临床意义。在这项为期14年的回顾性研究中，我们收集了108例MN患者的数据，并评估了临床病程、PLA 2 R-Ab和PLA 2 R-Ag之间的关系。我们还评估了THSD 7A状态。85例患者患有原发性MN（PMN），23例患者患有继发性MN。中位随访时间为30.4个月[四分位距，17.7;56.7]。在77例PMN和可用血清和/或活检的患者中，69例（89.6%）具有PLA 2 R相关疾病，如抗PLA 2 R-Ab和/或PLA 2 R-Ag所示，而8例（8/77，10.4%）两者均为阴性。两组在诊断时的年龄和通过蛋白尿、血清白蛋白水平和eGFR评估的结局方面无显著差异。8例阴性患者中有2例为THSD 7A阳性。在PLA 2 R相关PMN患者中，较年轻、较低的蛋白尿、较高的eGFR和较低的PLA 2 R-Ab水平在基线和6个月后与蛋白尿缓解相关。初始PLA 2 R-Ab滴度≤ 97.6 RU/mL和6个月内PLA 2 R-Ab完全耗尽与随访结束时的自发缓解显著相关。在利妥昔单抗治疗的患者中，治疗开始时较低的PLA 2 R-Ab滴度，以及3个月时PLA 2 R-Ab的缺乏和较高的血清白蛋白水平与缓解显著相关。值得注意的是，81.8%达到缓解的患者完全清除了PLA 2 R-Ab。PLA 2 R-Ab的耗竭和血清白蛋白水平的升高先于蛋白尿的减少。PLA 2 R自身免疫的评估对于患者管理至关重要。PLA 2 R-Ab和PLA 2 R-Ag的组合增加诊断灵敏度。PLA 2 R-Ab滴度是初始评估时疾病严重程度的生物标志物，并且抗体的动力学与疾病演变显著相关。
Clinical course of membranous nephropathy (MN) is difficult to predict. Measurement of circulating anti-PLA2R autoantibodies (PLA2R-Ab) and detection in immune deposits of PLA2R antigen (PLA2R-Ag) are major advances in disease understanding. We evaluated the clinical significance of these biomarkers. In this 14-year retrospective study, we collected data from 108 MN patients and assessed the relationship between clinical course, PLA2R-Ab and PLA2R-Ag. We also assessed THSD7A status. Eighty-five patients suffered from primary MN (PMN) and 23 patients from a secondary form. The median follow-up was 30.4 months [interquartile range, 17.7;56.7]. Among the 77 patients with PMN and available serum and/or biopsy, 69 (89.6%) had PLA2R-related disease as shown by anti-PLA2R-Ab and/or PLA2R-Ag, while 8 patients (8/77, 10.4%) were negative for both. There was no significant difference between these two groups in age at diagnosis and outcome assessed by proteinuria, serum albumin level and eGFR. Two of the 8 negative patients were positive for THSD7A. In patients with PLA2R related PMN, younger age, lower proteinuria, higher eGFR, and lower PLA2R-Ab level at baseline and after 6 months were associated with remission of proteinuria. Initial PLA2R-Ab titer ≤ 97.6 RU/mL and complete depletion of PLA2R-Ab within 6-months were significantly associated with spontaneous remission at the end of follow-up. In rituximab treated patients, lower PLA2R-Ab titer at initiation of treatment, and absence of PLA2R-Ab and higher serum albumin level at 3 months were significantly associated with remission. Noticeably, 81.8% of the patients who achieved remission completely cleared PLA2R-Ab. Depletion of PLA2R-Ab and increase of serum albumin level preceded the decrease of proteinuria. Assessment of PLA2R autoimmunity is essential for patient management. Combination of PLA2R-Ab and PLA2R-Ag increases diagnosis sensitivity. PLA2R-Ab titer is a biomarker of disease severity at initial assessment, and the kinetics of the antibody are significantly correlated to disease evolution.