Novel ELISA for thrombospondin type 1 domain-containing 7A autoantibodies in membranous nephropathy
Novel ELISA for thrombospondin type 1 domain-containing 7A autoantibodies in membranous nephropathy
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DOI：
10.1016/j.kint.2018.10.024
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发表时间：
2019-03-01
影响因子：
19.6
通讯作者：
Lambeau, Gerard
中科院分区：
文献类型：
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作者：
Zaghrini, Christelle;Seitz-Polski, Barbara;Lambeau, Gerard
抗磷脂酶A2受体1(PLA2R1)和凝血酶敏感蛋白1型结构域7A(THSD7A)的自身抗体是膜性肾病(MN)分型和预测疗效或治疗反应的生物标志物。免疫印迹和间接免疫荧光试验(IIFT)检测抗THSD7A自身抗体。在这里，我们建立了一种灵敏的酶联免疫吸附试验(ELISA)，优化了抗THSD7A自身抗体的定量检测。在来自6个队列的1012例经活检证实的MN患者中，28例THSD7A阳性患者经ELISA法鉴定，患病率为2.8%。通过筛查其他患者，其中大多数是因为PLA2R1无关的MN而转诊的，我们确定了另外21例患者，建立了49名THSD7A阳性患者的队列。28名患者(57%)是男性，男性患者比女性患者年龄大(67岁对49岁)。8例患者有恶性肿瘤史，但仅3例在MN诊断后2年内被诊断为恶性肿瘤。我们比较了EL ISA、IIFT、Western印迹和活检染色的结果，发现EL ISA和IIFT滴度有显著的相关性。抗THSD7A自身抗体在所有患者中以IgG4为主。8例THSD7A和PLA2R1双阳性。抗THSD7A自身抗体水平与疾病活动性和治疗反应相关。基线滴度高的患者临床结果较差。在一组具有连续滴度的患者中，在治疗无效或未实现缓解的患者中，观察到持续升高的抗THSD7A自身抗体。结论：新型抗THSD7A抗体可用于THSD7A相关MN患者的鉴别和治疗过程中自身抗体滴度的监测。
Autoantibodies against phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain-containing 7A (THSD7A) are emerging as biomarkers to classify membranous nephropathy (MN) and to predict outcome or response to treatment. Anti-THSD7A autoantibodies are detected by Western blot and indirect immunofluorescence test (IIFT). Here, we developed a sensitive enzyme-linked immunosorbent assay (ELISA) optimized for quantitative detection of anti-THSD7A autoantibodies. Among 1012 biopsy-proven MN patients from 6 cohorts, 28 THSD7A-positive patients were identified by ELISA, indicating a prevalence of 2.8%. By screening additional patients, mostly referred because of PLA2R1-unrelated MN, we identified 21 more cases, establishing a cohort of 49 THSD7A-positive patients. Twenty-eight patients (57%) were male, and male patients were older than female patients (67 versus 49 years). Eight patients had a history of malignancy, but only 3 were diagnosed with malignancy within 2 years of MN diagnosis. We compared the results of ELISA, IIFT, Western blot, and biopsy staining, and found a significant correlation between ELISA and IIFT titers. Anti-THSD7A autoantibodies were predominantly IgG4 in all patients. Eight patients were double positive for THSD7A and PLA2R1. Levels of anti-THSD7A autoantibodies correlated with disease activity and with response to treatment. Patients with high titer at baseline had poor clinical outcome. In a subgroup of patients with serial titers, persistently elevated anti-THSD7A autoantibodies were observed in patients who did not respond to treatment or did not achieve remission. We conclude that the novel anti-THSD7A ELISA can be used to identify patients with THSD7A-associated MN and to monitor autoantibody titers during treatment.