IgG4水平在磷脂酶A2受体相关膜性肾病病情活动及疗效判断中的临床意义

Clinical Significance of IgG4 Level in Predicting the Activity and Outcome of Phospholipase A2 Receptor-associated Membranous Nephropathy

目的 探讨IgG4作为反映磷脂酶A2受体相关膜性肾病(PLA2R-MN)病情活动和治疗预后生物学指标的可能性。方法 选取2017年4月至2018年1月杭州市中医院肾内科经肾活检确诊的PLA2R-MN患者56例、继发性膜性肾病(SMN)患者13例和IgA肾病(IgAN)患者10例,收集血尿标本,采用夹心酶联免疫吸附法检测血、尿IgG4水平。结果 PLA2R-MN患者血中位IgG4/IgG比值显著高于SMN(P=0.009)及IgAN患者(P<0.001);尿中位IgG4/肌酐比值显著高于SMN患者(P=0.008)。PLA2R-MN中肾功能不全患者的血中位IgG4/IgG比值及尿中位IgG4/肌酐比值均显著高于肾功能正常组(P=0.049,P=0.015)。PLA2R-MN中血清白蛋白<30 g/L患者组的血中位IgG4/IgG比值显著高于血清白蛋白≥30 g/L组(P=0.005)。53例PLA2R-MN患者随访观察至少1年,缓解组血清IgG4/IgG比值明显低于未缓解组(P=0.005)。其中23例缓解的患者血中位比值从治疗前的5.82%(4.54%,10.20%)降至2.91%(2.11%,5.37%)(P<0.001)。受试者工作特征曲线分析提示PLA2R-MN的血IgG4/IgG比值<10.24%有更高的缓解趋势(P=0.005)。结论 血及尿IgG4可能反映特发性膜性肾病病情活动和治疗预后。

Objective To investigate the feasibility of IgG4 as a biomarker of the activity and outcome of phospholipase A2 receptor(PLA2 R)-associated membranous nephropathy(PLA2 R-MN).Methods Serum and urine samples were collected from 56 patients with PLA2 R-MN,13 patients with secondary membranous nephropathy(SMN),and 10 patients with primary IgA nephropathy(IgAN) when kidney biopsy was performed in the Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine from April 2017 to January 2018.Sandwich enzyme-linked immunosorbent assay was employed to measure the serum and urinary IgG4 levels. Results The PLA2 R-MN group had higher median serum IgG4/IgG ratio than the SMN group(P=0.009) and the IgAN group(P<0.001) and higher median urinary IgG4/creatinine ratio than the SMN group(P=0.008).In the patients with PLA2 R-MN,the median serum IgG4/IgG ratio and urinary IgG4/creatinine ratio were significantly higher in the renal insufficiency group than in the normal renal function group(P=0.049,P=0.015).Moreover, the median serum IgG4/IgG ratio was higher in those with a serum albumin level<30 g/L than in those with a serum albumin level ≥30 g/L(P=0.005).Fifty-three patients with PLA2 R-MN were followed up for at least 1 year, and the serum IgG4/IgG ratios of the patients in remission were lower than those of the patients without remission(P=0.005).The median serum IgG4/IgG ratio of 23 patients in remission decreased from 5.82%(4.54%,10.20%)(at initial enrollment) to 2.91%(2.11%,5.37%)(after 1-year follow up) in remission patients(P<0.001).The receiver operating characteristic curve showed that the patients with a serum IgG4/IgG ratio<10.24% had a higher possibility of remission(P=0.005).Conclusion Serum and urinary IgG4 levels may be an indicator of the activity in PLA2 R-MN patients and thus may be a predictive biomarker of the outcomes.