不典型膜性肾病患者血清M型磷脂酶A2受体抗体及肾组织IgG亚型分布的研究

Anti-PLA2R autoantibodies in serum and IgG subclass deposits on glomeruli in undetermined atypical membranous nephropathy

目的通过检测不明原因的不典型膜性肾病（UAMN）患者血清中M型磷脂酶A2受体（PLA2R）抗体及肾组织中IgG亚型的分布，研究UAMN患者血清中PLA2R抗体及肾组织中IgG亚型的分布特点。方法人选2004年2月至2011年11月于北京大学人民医院肾内科诊断为UAMN的患者20例。对照组包括特发性膜性肾病（IMN）患者20例，继发性膜性肾病（SMN）患者13例。其中SMN组中包括狼疮膜性肾病（LMN）5例，乙肝病毒相关性膜性肾病（HBV-MN）8例。分析入选患者的临床及病理资料，检测血清PLA2R抗体及肾组织中IgG亚型的分布特点。结果（1）UAMN组患者肾活检时平均年龄为（37．9±3．8）岁，IMN组为（50．1±3．0）岁，SMN组为（49．5±4．5）岁，其中UAMN组平均年龄显著低于IMN组（P=0．0178）。UAMN组、IMN组和SMN组的女／男比例分别为0．8：1、0．7：1和0．6：1，差异无统计学意义。（2）与SMN组比较，UAMN组24h尿蛋白定量更低（3．47g比7．89g，P=0．023），大量蛋白尿患者的比例也更低（50．0％比84．6％，P=0．043），血清IgG水平更低[（8．40±3．58）g／L比（10．09±4．69）g／L，P=0．025]，血清ANA阳性率也更低（10．0％比53．8％，P=0．006）。人血白蛋白、血肌酐、eGFR、血清HBsAg阳性率、血清HBeAg阳性率、血清抗HCV阳性率以及低白蛋白血症、肾病综合征患者比例在3组中的差异均无统计学意义。（3）。肾脏病理免疫荧光结果示，与IMN组比较，UAMN组IgA、IgM和C1q荧光阳性率更高，差异有统计学意义（均P〈0．01）；与SMN组比较，则两组的IgA、IgG、IgM、C1q和c3荧光阳性率及荧光强度差异均无统计学意义。（4）在所有53例患者血清中，仅有10例IMN组患者血清抗PLA2R自身抗体检测为阳性，在IMN组PLA2R自身抗体检出率为50％。3组间的PLA2R自身抗体检出率差异有统计学意义（P〈0．01）。（5）对肾组织IgG亚型的检测：UAMN组中IgG1亚型阳性率最高（40％），IgG3亚型阳性率最低（15％）。IMN组中，IgG4亚型阳性率最高（60％），其次为IgG1（15％），IgG2及IgG3亚型阳性率最低（均为5％）。SMN组中，IgG1亚型阳性率最高（76．9％），IgG4亚型阳性率最低（30．8％）。UAMN组IgG1、IgG3亚型阳性率与IMN及SMN组比较差异均无统计学，IgG2亚型阳性率表现出与SMN组差异有统计学意义（30．0％比69．2％，P〈0．05），IgG4亚型阳性率与IMN组差异有统计学意义（20％比60％，P〈0．05）。SMN组IgG1、IgG2和IgG3亚型的阳性率均显著高于IMN组（分别为76．9％、69．2％、46．2％比15％、5％、5％，均P〈0．01）。IMN组IgG4亚型在。肾小球沉积的阳性率高于SMN及UAMN组，但仅与UAMN组差异具统计学意义（P=0．0225）。UAMN组显示出了与IMN及SMN组的不同，更类似于SMN组特点。结论UAMN组患者抗PLA2R自身抗体检测均为阴性，肾组织以IgG1亚型沉积为主，表现了类似SMN的特点，但在临床指标上又显示了与SMN的不同。因此要加强临床的长期随访,深入对这一类疾病的研究。

Objective To investigate the characteristic of autoantibodies of M- type phospholipase A2 receptor （PLA2R） in serum and the glomerular IgG subclass deposits in undetermined atypical membranous nephropathy （MN） patients. Methods From Feb 2004 to Nov 2011, 53 cases diagnosed as MN by kidney puncture biopsy in our hospital were included into the study. There were 20 undetermined atypical membranous nephropathy （UAMN）, 20 idiopathic membranous nephropathy （IMN） and 13 secondary membranous nephropathy （SMN） which were composed of lupus membranous nephropathy （LMN） and HBV related membranous nephropathy （HBV-MN）. Clinlical and pathological characteristics were analyzed. The autoantibodies of PLA2R in serum were detected and the glomerular IgG subclass deposits were observed. Results （1） The average age underwent renal biopsy was （37.9±3.8） years of UAMN, （50.1±3.0） years of IMN and （49.5±4.5） years of SMN. The difference in onset average age at disease was significant between UAMN and IMN （P = 0.0178）. The female/male ratio （F/M） in UAMN, IMN and SMN was 0.8： 1, 0.7：1 and 0.6： 1（P〉 0.05）. （2） Compared with SMN, the level of 24-hours urinary protein excretion （3.47 g vs 7.89 g, P = 0.023）, the ratio of amount urinary protein patients （50.0% vs 84.6%, P = 0.043）, the level of serum IgG [（8.40±3.58） g/L vs （10.09±4.69） g/L, P = 0.025] and the positive rate of ANA in serum （10.0% vs 53.8%, P = 0.006） in UAMN were all much lower. There were no significant statistical differences in serum albumin, serum creatinine, eGFR, positive rate of HBsAg, HBeAg or HCV, as well as the ratio of hypo- albuminemia and nephrotic syndrome among the three groups. （3） IF positive rate of IgA, IgM and Clq in UAMN were all significantly higher than that in IMN （P 〈 0.01）. There were no significant differences in IF positive rate of IgA, IgM, Clq, IgG and C3 between UAMN and SMN. The IF strength of IgA, IgG, IgM, C3 and Clq in UAMN showed no significant differences between UAMN and SMN. （4） The serum autoantibodies of PLA2R were only detected in 10 eases of IMN group （50%） with all the other eases negative. This detection rate of serum autoantibodies of PLA2R showed significant statistical differences among the three groups （P 〈 0.01）, but no differences between UAMN and SMN （the detection rate in both groups were 0%）. （5） IgG1 deposits was the dominant IgG on the glomeruli in UAMN group （40%）, as well as in SMN group （76.9%）. IgG4 deposits was the dominant IgG on the glomeruli in IMN group （60%）. The positive rate of IgG1 and IgG3 in UAMN showed no significant statistical differences when compared with IMN or SMN. The positive rate of IgG2 in UAMN was significantly lower than in SMN （30.0% vs 69.2%, P 〈 0.05）. The positive rate of IgG4 in UAMN was significantly lower than in IMN （20% vs 60%, P 〈 0.05）. The positive rate of IgG1, IgG2 and IgG3 in SMN were all significantly higher than in IMN. Conclusions None of the UAMN group had autoantibodies of PLA2R in serum, and IgG1 deposits was the dominant IgG subclass on the glomeruli which indicated the similarity with the SMN group. At the same time, UAMN was significantly different from SMN in clinical manifestations.