Microbiology Institute, ASST Santi Paolo e Carlo, S. Carlo Borromeo Hospital, Milan, Italy.
Renal Unit, Department of Medicine and Surgery, University of Milano-Bicocca and ASST Monza, Monza, MB, Italy.
J Nephrol. 2018 Apr;31(2):271-278. doi: 10.1007/s40620-017-0451-5. Epub 2017 Oct 28.
Autoantibody against phospholipase A2 receptor (anti-PLA2R) is a sensitive and specific biomarker of idiopathic membranous nephropathy (iMN), being found in approximately 70% of iMN patients and only occasionally in other glomerular diseases. However, whereas its diagnostic specificity vs. normal controls and other glomerulonephritides (GN) has been firmly established, its specificity vs. membranous nephropathy associated with various diseases (sMN) has given inconsistent results. The aim of our study was to evaluate the prevalence of anti-PLA2R antibodies in iMN in comparison with various control groups, including sMN. A total of 252 consecutive iMN patients, 184 pathological and 43 healthy controls were tested for anti-PLA2R antibody using indirect immunofluorescence (PLA2R IIFT, Euroimmun). Anti-PLA2R autoantibodies were detectable in 178/252 iMN patients, 1/80 primary GN, 0/72 secondary GN, 9/32 sMN and 0/43 healthy controls, with a diagnostic sensitivity of 70.6%. The diagnostic specificity of anti-PLA2R antibody vs. normal and pathological controls was 100 and 94.6% respectively. However, when the diagnostic specificity was calculated only vs. secondary forms of MN, it decreased considerably to 71.9%. Interestingly enough, 9 out of 10 anti-PLA2R positive patients in the disease control groups had membranous nephropathy associated with various diseases (7 cancer, 1 Crohn's disease, 1 scleroderma). In conclusion, anti-PLA2R positivity in a patient with MN, should not be considered sufficient to abstain from seeking a secondary cause, especially in patients with risk factors for neoplasia. The causal relationship between tumors and anti-PLA2R-induced MN remains to be established, as well as the possible mechanisms through which malignancies provoke autoimmunity.
抗磷脂酶 A2 受体（anti-PLA2R）自身抗体是特发性膜性肾病（iMN）的一种敏感且特异的生物标志物，约 70%的 iMN 患者中可检测到该抗体，而在其他肾小球疾病中则很少见。然而，虽然其相对于正常对照和其他肾小球肾炎（GN）的诊断特异性已得到明确证实，但相对于各种疾病相关膜性肾病（sMN）的特异性则得出了不一致的结果。我们的研究目的是评估 iMN 患者中抗 PLA2R 抗体的患病率，并与包括 sMN 在内的各种对照组进行比较。共检测了 252 例连续的 iMN 患者、184 例原发性 GN、72 例继发性 GN、32 例 sMN 和 43 例健康对照者的抗 PLA2R 抗体，采用间接免疫荧光法（PLA2R IIFT，Euroimmun）进行检测。在 252 例 iMN 患者中有 178 例可检测到抗 PLA2R 自身抗体，在 80 例原发性 GN 中有 1 例，在 72 例继发性 GN 中有 0 例，在 32 例 sMN 中有 9 例，在 43 例健康对照中有 0 例，诊断灵敏度为 70.6%。抗 PLA2R 抗体相对于正常和病理对照的诊断特异性分别为 100%和 94.6%。然而，当仅计算其相对于继发性 MN 形式的诊断特异性时，其显著下降至 71.9%。有趣的是，在疾病对照组中，10 例抗 PLA2R 阳性患者中有 9 例均患有与各种疾病相关的膜性肾病（7 例癌症、1 例克罗恩病、1 例硬皮病）。总之，在 MN 患者中出现抗 PLA2R 阳性，不应认为足以排除寻找继发性病因，尤其是在存在肿瘤发生风险因素的患者中。肿瘤与抗 PLA2R 诱导的 MN 之间的因果关系仍有待确定，以及恶性肿瘤引发自身免疫的可能机制也有待确定。
