Kidney Transplantation Complications Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Student research committee, Mashhad University of Medical Sciences, Mashhad, Iran.
BMC Nephrol. 2021 Apr 19;22(1):138. doi: 10.1186/s12882-021-02338-6.
Although IgG4 deposit against phospholipase A2 receptor (anti-PLA2R) is predominantly presented in the renal biopsy of patients with primary membranous nephropathy (MN), its diagnostic value of this immune complex has not been fully established.
In this cohort study, 108 biopsy-proven MN patients with proteinuria were evaluated during two years follow up and were divided into primary and secondary groups. Renal biopsy specimens were pathologically assessed for IgG4 and PLA2R depositions by immunohistochemistry (IHC). Therefore, the relationships between staining severity, MN type and total proteinuria in all patients were determined.
Of 108 patients, 73.1% had primary MN and 26.9% were diagnosed as secondary form. IHC staining in patients with primary MN was positive for PLA2R in 76 (96.2%) and IgG4 in 68 (86.1%). Cases with positive PLA2R expression had a significantly higher rate among patients with mild to moderate stages (P = 0.03). No significant relationship was found between intensity of PLA2R and IgG4 deposits with proteinuria and serum creatinine. Based on our data, double positivity/negativity of PLA2R and IgG4 expression adds prominent information to the clinical data and were found to be useful and robust biomarkers for detection of primary MN patients with high sensitivity and specificity (97.1 and 96.3% respectively, PPV = 98.5% and NPV = 92.9%).
Simultaneously expression of PLA2R and IgG4 in renal biopsy specimens of patients with MN could possibly be used as a potential diagnostic method to distinguish primary from secondary MN and also pathological severity of the disease.
尽管 IgG4 沉积针对磷脂酶 A2 受体（抗-PLA2R）主要见于原发性膜性肾病（MN）患者的肾活检，但该免疫复合物的诊断价值尚未完全确定。
在这项队列研究中，对 108 例经活检证实的蛋白尿 MN 患者进行了两年的随访评估，并分为原发性和继发性两组。通过免疫组织化学（IHC）对肾活检标本进行 IgG4 和 PLA2R 沉积的病理评估。因此，确定了所有患者中染色严重程度、MN 类型和总蛋白尿之间的关系。
在 108 例患者中，73.1%为原发性 MN，26.9%为继发性。原发性 MN 患者的 IHC 染色 PLA2R 阳性 76 例（96.2%），IgG4 阳性 68 例（86.1%）。表达 PLA2R 阳性的病例在轻度至中度阶段的患者中具有更高的阳性率（P=0.03）。PLA2R 和 IgG4 沉积的强度与蛋白尿和血清肌酐之间未发现显著关系。根据我们的数据，PLA2R 和 IgG4 表达的双重阳性/阴性为临床数据增加了重要信息，并且被发现是检测原发性 MN 患者的有用且稳健的生物标志物，具有高灵敏度和特异性（分别为 97.1%和 96.3%，PPV=98.5%，NPV=92.9%）。
MN 患者肾活检标本中 PLA2R 和 IgG4 的同时表达可能可作为一种潜在的诊断方法，用于区分原发性和继发性 MN，以及疾病的病理严重程度。
