M型磷脂酶A2受体及1型血小板反应蛋白7A域在特发膜性肾病中的临床意义

Clinical significance of M-type phospholipase A2 receptor and thrombospondin Type 1 domaincontaining 7A in primary membranous nephropathy

目的:探讨M型磷脂酶A2受体(phospholipase A2 receptor,PLA2R)、1型血小板反应蛋白7A域(thrombospondin Type 1 domain-containing 7A,THSD7A)及相应的抗体对特发性膜性肾病(primary membranous nephropathy,PMN)的诊断价值及其血清抗体水平与预后的关系。方法:纳入2015年2月至2017年8月中南大学湘雅二医院肾内科行肾活检确诊的膜性肾病128例,其中PMN108例(PMN组),继发性膜性肾病(secondary membranous nephropathy,SMN)20例(SMN组)。应用间接免疫荧光法检测肾组织PLA2R抗原表达,间接免疫荧光法和免疫组织化学法检测肾组织THSD7A抗原表达,ELISA检测血清PLA2R和THSD7A的抗体水平。根据检测结果,又将患者分为PLA2R相关性膜性肾病组和THSD7A相关性膜性肾病组。结果:PMN组肾小球PLA2R阳性率明显高于SMN组(分别为72%和35%,P<0.01),PMN组血清PLA2R抗体阳性率亦明显高于SMN组(分别为50%和25%,P<0.05)。PMN组血清PLA2R抗体与24 h尿蛋白量呈正相关关系(r=0.254,P<0.05),与血清白蛋白呈负相关关系(r=-0.236,P<0.05)。PMN组中7例(6%)患者肾小球THSD7A呈阳性,SMN组有1例(5%)患者肾小球THSD7A呈阳性。PMN组血清THSD7A抗体水平明显高于SMN组[分别为(0.49±0.26)和(0.34±0.27)pg/mL,P<0.05]。7例THSD7A相关性膜性肾病组与86例PLA2R相关性膜性肾病组的临床病理特征差异均无明显统计学意义(均P>0.05)。结论:肾组织PLA2R和THSD7A是PMN的靶抗原,其血清抗体有助于PMN的鉴别诊断;PLA2R抗体水平可反映病情严重程度,可用来评估治疗效果;PMN患者THSD7A相关性膜性肾病的发病率低,监测血清THSD7A抗体水平可评估患者病情,并可预测疾病转归。

Objective: To evaluate the value of thrombospond in Type Ⅰ domain-containing 7A(THSD7A) and M-type phospholipase A2 receptor(PLA2R) in primary membranous nephropathy(PMN) and to explore the relationship between their antibody levels and prognosis.Methods: Renal tissues in 128 patients with membranous nephropathy in the Second Xiangya Hospital of Central South University were collected from February 2015 to August 2017, including 108 patients with primary membranous nephropathy(PMN group)and 20 patients with secondary membranous nephropathy(SMN)(SMN group). Indirect immunofluorescence method was used to detect the expression of PLA2R antigen in kidney tissues, and the glomerular expression of THSD7A antigen was examined by immunohistochemistry and indirect immunofluorescence. The serum levels of anti-PLA2R antibodies and THSD7A antibodies were also detected by ELISA. According to the results of PMN examination, the patients were also divided into a PLA2R-related membranous nephropathy group and a THSD7A-related membranous nephropathy group.Results: The positive rate of PLA2R in the renal tissues in the PMN group was higher than that in the SMN group(78% in the PMN group, 35% in the SMN group, P<0.01),while the positive rate of anti-PLA2R antibody in the PMN group was also higher than that in the SMN group(50% in the PMN group, 25% in the SMN group, P<0.05). The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein(r=0.254,P<0.05) and negatively correlated with serum albumin(r=-0.236, P<0.05). The expression of THSD7A was positive in glomeruli in 7 cases of the PMN group(6%) by immunohistochemistry, and which was positive in 1 case of the SMN group(5%).The serum levels of anti-THSD7A antibody in the PMN group were higher than those in the SMN group[(0.49±0.26) pg/m L in the PMN group,(0.34±0.27) pg/m L in the SMN group, P<0.05].There was no difference in the clinical characteristics between the PLA2R-related membranous nephropathy group and the THSD7A-related membranous nephropathy group.Conclusion: PLA2R and THSD7A are the target antigen of PMN, and the associated autoantibodies are helpful for the differential diagnosis of PMN. The anti-PLA2R antibody levels can reflect the severity of the disease and evaluate the effect of treatment. The incidence of THSD7A membranous nephropathy is low, and monitoring the serum antiTHSD7A antibody levels can assess patients’ condition and predict disease outcome.