IgG4相关性小管间质性肾炎诊断标准分析及致病机制探讨  

Analysis of diagnostic criteria and pathogenesis of Ig G4-related tubulointerstitial nephritis

作　　者：汤绚丽[1] 杜园园[1] 林宜[1] 郑洁[1] 朱晓玲[1] 胡云琴[1] TANG Xuanli;DU Yuanyuan;LIN Yi;ZHENG Jie;ZHU Xiaoling;HU Yunqin(Department of Nephrology,Hangzhou Hospital of Traditional Chinese Medicine,Hangzhou 310007,China)

机构地区：[1]杭州市中医院肾内科(浙江省肾脏疾病防治技术研究重点实验室),310007

出　　处：《浙江医学》2018年第14期1558-1561,1654,共5页Zhejiang Medical Journal

基　　金：杭州市卫生科技计划项目(2015A36);杭州市科技发展计划项目(20163501Y41)

摘　　要：目的回顾性筛选符合IgG4相关性小管间质性肾炎(IgG4-TIN)诊断标准的病例,分析诊断标准的适用范围,并探讨其致病机制。方法选取肾间质较多浆细胞浸润的肾穿刺标本,免疫组化法检测CD138、IgG4、IgG阳性细胞数,并根据美国梅奥诊所及日本JSN协会提出的诊断标准,筛选出IgG4-TIN的疑似及确诊病例。同时用免疫组化法检测肾间质转化生长因子β(TGF-β)、NF-κB的表达情况,探讨IgG4阳性细胞致炎、致纤维化的机制。结果通过CD138、IgG4及IgG染色筛选出病理疑似病例28例,依据美国梅奥诊断标准筛选出高度可疑IgG4-TIN病例15例。这些病例不论临床、病理表现或IgG4阳性细胞数量及分布情况均存在较大异质性,因此进一步采用日本JSN协会推荐的更为严格的诊断标准,确诊IgG4-TIN病例4例。从致病机制上看,病理疑似组TGF-β与IgG4阳性细胞数存在强的正相关性(r=0.413,P<0.05)。结论符合美国梅奥诊断标准的病例应视为高度可疑IgG4-TIN,而确诊需要日本JSN协会标准进一步验证。浆细胞分泌过多的IgG4可能通过刺激TGF-β因子表达及NF-κB信号途径导致纤维化及免疫紊乱。Objective To screen IgG4-related tubulointerstitial nephritis(IgG4-TIN)in archived renal biopsy samples and to analyze proposed diagnostic criteria and its pathogenesis. Methods Kidney biopsy samples with increased plasma cell infiltration were screened and the expression of CD138,IgG and IgG4 was assayed by immunohistochemical staining.Suspected and confirmed diagnosis of IgG4-TIN were performed by proposed criteria from the Mayo Clinic and Japanese Society of Nephnology(JSN),respectively.The expressions of TGF-βand NF-κB were detected in inflammation area of samples by immunohistochemistry. Results Twenty eight suspected IgG4-TIN cases were diagnosed by CD138,IgG and IgG4 staining and histological criteria(IgG4 positive cells>10/HPF or IgG4/IgG positive cells>40%).Fifteen highly suspected IgG4-TIN cases were then screened according to the Mayo Clinic criteria,in which there was great heterogeneity in clinical or pathological characteristics.Therefore,the JSN criteria were applied and 4 cases were confirmed as IgG4-TIN finally.TGF-βhad significant correlation with the number of IgG4 positive cells(r=0.413,P<0.05). Conclusion Cases meeting the Mayo Clinic criteria should be treated as highly suspected IgG4-TIN,and the diagnosis should be confirmed by JSN criteria.Over secreted IgG4 from plasma cells might up-regulate TGF-βexpression and stimulate NF-κB signal pathway to induce fibrosis and cause immune disorder.

关 键 词：IgG4相关性小管间质性肾炎 诊断标准 免疫组化 致病机制 

分 类 号：R692.3[医药卫生—泌尿科学]