免疫球蛋白G4相关性膜性肾病6例特征分析及文献复习

Analysis of the characteristics of IgG4-related membranous nephropathy with literature review

目的回顾性分析6例免疫球蛋白(Ig)G4相关膜性肾病(IgG4-MN),结合文献复习探讨本病的临床及肾脏病理特征,提高临床医生对该病的认识。方法选取2017年4月至2021年1月在本院肾脏病中心经肾活检确诊为IgG4-MN的6例患者,同时系统性复习文献,总结临床病理特点。结果6例患者为男性,年龄55~75岁,尿蛋白(24 h)(3.1±2.2)g,3例(50%)呈肾病综合征,4例(67%)血清肌酐升高,肌酐(103±24)μmol/L,6例(100%)血清IgE水平升高,4例(67%)IgG4升高;1例(17%)肾组织抗磷脂酶A2受体(PLA2R)阳性,6例伴有肾小管间质炎症(TIN)。复习文献提示包括本院6例共计报道了49例IgG4-MN,男性40例(40/46,87%),年龄(61±12)岁,32例(32/49,65%)呈肾病综合征范围蛋白尿,血IgG和IgG4升高比例分别为61%(20/33)和88%(36/41);13例(13/15,87%)血清IgE水平升高,47%(14/30)出现低补体C3和44%(12/27)出现低补体C4;累及器官主要分布为胰腺(15/37),淋巴结(16/37);肾脏病理显示74%(36/49)伴有TIN;电子致密物沉积以上皮下沉积为主。血清抗PLA2R抗体阳性7%(2/28),肾组织PLA2R阳性17%(3/18),肾组织可疑阳性6%(1/18),两者同时阳性8%(1/12)。结论IgG4-MN通常表现为中老年患者肾病范围蛋白尿或肾病综合征,大部分合并TIN,伴其他器官受累;IgG4-MN中存在一定比例的PLA2R阳性,是原发性还是继发性MN,有待进一步研究。

Objective By retrospectively analyzing 6 cases of IgG4-related membranous nephropathy(IgG4-MN),combined with literature review,to explore the clinical and renal pathological characteristics of the disease,and improve clinicians'understanding of the disease.Methods The data of six patients with biopsy-proven IgG4-MN in the nephrology center of our hospital during April 2017 to January 2021 were collected.At the same time,we reviewed the literature systematically and summarized the clinicopathological characteristics.Results Six male patients with the age ranged fom 55 to 75 years old were described.Urine protein level was(3.1±2.1)g/24 h,3 cases(50%)showed nephrotic syndrome and 4 cases(67%)had elevated serum creatinine.The median creatinine level was(103±24)μmol/L.Six cases(100%)had elevated serum immunoglobulin(Ig)E level,and 4 cases(67%)had elevated IgG4.M-type phospholipase A2 receptor(PLA2R)was positive in 1 case(17%)and tubulointerstitial nephritis(TIN)was present in 6 cases.The review of the literature suggested that a total of 49 cases with IgG4-MN were reported,including 6 cases in this report.There were 40 males(40/46,87%),with a age range of(61±12)years old,32 cases(32/49,65%)showed nephrotic syndrome range proteinuria,and the proportion of serum IgG and IgG4 increase was 61%(20/33)and 88%(36/41),respectively,13 cases(13/15,87%)had elevated serum IgE level,47%(14/30)had low-complement C3 and 44%(12/27)had low-complement C4 level.The main organs involved were pancreas(15/37)and lymph nodes(16/37).Renal pathology showed TIN in 74%(36/49).Electron dense deposition was mainly subepithelial deposits.7%(2/28)were positive for anti-PLA2R antibody in serum,17%(3/18)were positive for PLA2R in kidney tissue,6%(1/18)were suspected positive for PLA2R in kidney tissue,and 8%(1/12)were dual positive in blood and kidney tissue.Conclusion IgG4-MN usually presents with nephrotic range proteinuria or nephrotic syndrome in middle-aged and elderly patients.Most of them are complicated with TIN and other organ involvement.A certain proportion of patients are PLA2R positive in IgG4-MN,and whether it is primary or secondary MN needs further study.