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特发性膜性肾病中血清M型磷脂酶A2受体1的临床意义

Clinical significance of phospholipase A2 receptor 1 in patients with idiopathic membranous nephropathy

摘要:

目的 探讨血清M型磷脂酶A2受体1(PLA2R1)在诊断、鉴别诊断成人特发性膜性肾病(IMN)与判断病情中的作用.方法 以南方医科大学附属南方医院肾内科2015年3月至2016年1月经肾活检病理确诊的IMN、继发性膜性肾病(SMN)及其他肾小球疾病成人患者共242例为研究对象,包括IMN 90例、SMN 20例、IgA肾病(IgAN) 82例、微小病变型肾病(MCD)30例、局灶节段性肾小球硬化(FSGS)16例、膜增生性肾小球肾炎(MPGN)4例.收集所有患者的年龄、性别、血清肌酐、血清白蛋白、24h尿蛋白量等临床资料,酶联免疫吸附法测定血清PLA2R1滴度,间接免疫荧光法测定肾组织PLA2R1表达及IgG亚型.比较各组患者的血清PLA2R1阳性率,并分析其与临床病理指标之间的关系.结果 与IMN组患者比较,SMN、MCD、FSGS组患者均年龄较小(均P<0.01);IgAN组患者年龄小,血清白蛋白高,24 h尿蛋白量低(均P< 0.01);MPGN组患者Scr高(P<0.01).75.6%IMN患者血清PLA2R1阳性,SMN和其他肾小球疾病患者血清PLA2R1均为阴性.IMN患者血清PLA2R1与肾穿刺病理活检的诊断结果分布存在差异(配对卡方P< 0.001),阳性符合率为100%,阴性符合率为87.4%,总符合率达90.9%,一致性良好(Kappa=0.795,P<0.001).IMN组患者各IgG亚型与SMN组比较,仅IgG4中度以上阳性分布差异有统计学意义(82.2%比5.0%,P<0.001);IMN患者肾组织PLA2R1阳性率为41.1%,高于SMN患者的10.0% (P=0.009);IMN患者肾组织PLA2R1阳性伴IgG4中度以上阳性比例高于SMN患者(40.0%比0.0%,P<0.001),肾组织PLA2R1联合肾脏IgG亚型分析诊断IMN的特异性进一步提高.IMN患者血清PLA2R1和肾组织PLA2R1分布存在差异(配对卡方P< 0.001).IMN患者血清PLA2R1滴度与24 h尿蛋白定量呈正相关(r=0.315,P=0.002),与血清白蛋白呈负相关(r=-0.228,P=0.030),与血清肌酐相关性无统计学意义(r=0.199,P=0.059).结论 血清PLA2R1可作为诊断及鉴别诊断IMN的特征性生物学标志物,并可反映病情的严重程度.

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abstracts:

Objective To explore the role of phospholipase A2 receptor 1 (PLA2R1) in the diagnosis,differential diagnosis and evaluation of idiopathic membranous nephropathy (IMN) in adult patients.Methods A total of 242 renal disease patients diagnosed by renal biopsy from March 2015 to January 2016 were enrolled,consisting of 90 IMN,20 secondary membranous nephropathy (SMN),82 IgA nephropathy (IgAN),30 minimal changed disease (MCD),16 focal segmental glomerulosclerosis (FSGS) and 4 membranoproliferative glomerulonephritis (MPGN).Their clinical data including age,sex,serum creatinine (Scr),serum albumin and 24 h urinary protein were collected.Serum PLA2R1 was measured by enzyme linked immunosorbent assay.PLA2R and IgG subclasses in glomeruli were detected by indirect immunofluorescence assay.The positive rate of serum PLA2R1 among those groups and its correlation with clinical-pathological parameters were analyzed.Results Compared with IMN patients,SMN,MCD and FSGS patients were younger (all P < 0.01); IgAN patients were younger and had higher serum albumin and lower 24 h proteinuria (all P < 0.001); MPGN patients had higher Scr (all P < 0.01).The positive rate of serum PLA2R1 was 75.6% in IMN patients,while it was 0.0% in non-IMN patients.The distribution between serum PLA2R1 and pathological diagnosis had difference (P < 0.001),their positive coincidence rate was 100%,negative coincidence rate was 87.4%,total coincidence rate was 90.9% and their consistency was well (Kappa=0.795,P < 0.001).Among IgG subtype comparisons between IMN patients and SMN patients in the glomeruli,only moderate or more positive IgG4 had statistical differences (82.2% vs 5.0%,P < 0.001); the positive rate of glomerular PLA2R1 was 41.1% in IMN patients,higher than 10.0% in SMN patients (P=0.009); positive PLA2R1 with moderate or more positive IgG4 in glomeruli in IMN patients was more than that in SMN patients (40.0% vs 0.0%,P < 0.001),which could improve the diagnostic specificity of IMN.In IMN patients serum PLA2R1 and glomerular PLA2R1 had statistical differences (P<0.001).Spearman rank correlation analysis showed that serum PLA2R1 of IMN patients positively correlated with 24 h proteinuria (r=0.315,P=0.002),negatively correlated with serum albumin (r=-0.228,P=0.030) and didn't correlate with Scr (r=0.199,P=0.059).Conclusions Serum PLA2R can be used as the specific indicator for diagnosis,differential diagnosis of IMN and to reflect the severity of IMN in patients.

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