Detection of PLA2R Autoantibodies before the Diagnosis of Membranous Nephropathy
Detection of PLA2R Autoantibodies before the Diagnosis of Membranous Nephropathy
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DOI：
10.1681/asn.2019050538
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发表时间：
2020-01-01
影响因子：
13.6
通讯作者：
Olson, Stephen W.
中科院分区：
文献类型：
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作者：
Burbelo, Peter D.;Joshi, Megha;Olson, Stephen W.
抗M型磷脂酶A2受体（PLA 2 R-AB）的循环血清自身抗体是诊断和监测原发性膜性肾病（MN）的关键生物标志物。然而，鲜为人知的是，PLA 2 R-AB的外观和轨迹之前的临床诊断MN。方法使用国防部血清库，我们分析了PLA 2 R-AB在多个，1054纵向血清样本收集前诊断MN从134个人与原发性MN，35个人与继发性MN，和134名健康志愿者。我们评估的存在和时间的非肾病范围蛋白尿（NNRP）和血清白蛋白测量相关的PLA 2 R-AB status.Results分析的PLA 2 R-AB在纵向血清样本显示血清阳性44%（59 134）的原发性MN病例，3%（35）继发性MN病例，并在0%的健康对照。在MN患者中，在肾活检诊断前的中位274天（四分位距，71-821天）即可检测到PLA 2 R-AB。大约三分之一的参与者在MN诊断的3个月内成为血清阳性。在21例确诊前NNRP的患者中，43%（21例中有9例）在NNRP首次确诊前血清学阳性，28.5%（21例中有6例）在NNRP同时血清学阳性; 66%（59例中有39例）的PLA 2 R-AB血清学阳性患者在最初检测到抗体时存在低白蛋白血症。12名参与者（20%）血清反应阳性前低白蛋白血症变得明显，和8名参与者（14%）血清反应阳性后低白蛋白血症变得apparent.Conclusions循环PLA 2 R-AB检测数月至数年前记录NNRP和活检证实诊断MN患者。
Background Circulating serum autoantibodies against the M-type phospholipase A2 receptor (PLA2R-AB) are a key biomarker in the diagnosis and monitoring of primary membranous nephropathy (MN). However, little is known about the appearance and trajectory of PLA2R-AB before the clinical diagnosis of MN.Methods Using the Department of Defense Serum Repository, we analyzed PLA2R-AB in multiple, 1054 longitudinal serum samples collected before diagnosis of MN from 134 individuals with primary MN, 35 individuals with secondary MN, and 134 healthy volunteers. We evaluated the presence and timing of non-nephrotic range proteinuria (NNRP) and serum albumin measurements in relation to PLA2R-AB status.Results Analysis of PLA2R-AB in longitudinal serum samples revealed seropositivity in 44% (59 out of 134) of primary MN cases, 3% (one out of 35) of secondary MN cases, and in 0% of healthy controls. Among patients with MN, PLA2R-AB were detectable at a median of 274 days before renal biopsy diagnosis (interquartile range, 71-821 days). Approximately one third of the participants became seropositive within 3 months of MN diagnosis. Of the 21 individuals with documented prediagnostic NNRP, 43% (nine out of 21) were seropositive before NNRP was first documented and 28.5% (six out of 21) were seropositive at the same time as NNRP; 66% (39 out of 59) of those seropositive for PLA2R-AB had hypoalbuminemia present at the time antibody was initially detected. Twelve participants (20%) were seropositive before hypoalbuminemia became apparent, and eight participants (14%) were seropositive after hypoalbuminemia became apparent.Conclusions Circulating PLA2R-AB are detectable months to years before documented NNRP and biopsyproven diagnosis in patients with MN.