IgG4相关肾小管间质性肾炎肾间质异位淋巴组织的病理学特征及其临床意义

Clinical significance and pathological features of ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis

目的探讨IgG4相关肾小管间质性肾炎(IgG4-related tubulointerstitial nephritis,IgG4-TIN)中肾间质淋巴细胞和浆细胞浸润及与之相关的异位淋巴组织形成的病理学特征和临床意义。方法回顾性收集2012年1月至2018年12月在北京大学第一医院肾内科经病理明确诊断为IgG4-TIN患者的病例资料,肾活检标本均进行常规的光镜、免疫荧光和电镜检查,利用免疫组化检测CD20、CD3、CD138的表达情况,同时对其肾小管间质病变进行半定量评估,探讨肾间质浸润的淋巴细胞的类型和分布特点,并分析其与临床病理特点的关系。结果共24例患者被纳入本研究,其中21例男性(87.5%),3例女性(12.5%);年龄(58.0±10.8)岁(38~75岁)。16例(66.7%)肾小管间质内可见异位生发中心样结构形成,表现为团灶状T细胞、B细胞聚集,浆细胞散在分布于聚集灶周边,聚集灶形成淋巴滤泡样结构,其内可见滤泡树突状细胞及中心母细胞样细胞;同时,19例(79.2%)肾间质浸润的浆细胞内可见Russell小体形成。相比肾间质无Russell小体形成的病例,肾间质浆细胞内有Russell小体形成的病例更容易出现异位生发中心样结构形成(P=0.001)、肾小管基底膜(TBM)电子致密物沉积(P=0.040)和血C3水平降低(P=0.028)。结论IgG4-TIN肾间质局部可形成异位生发中心样结构并伴有浆细胞内Russell小体形成,提示肾间质局部可能存在淋巴细胞和浆细胞的持续活化,并参与组织损伤的发生发展。

Objective To investigate the clinical significance and pathological features of lymphocytes and plasma cells infiltration and related ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis (IgG4-TIN). Methods Complete data was collected from 24 patients with IgG4-TIN confirmed by pathology in the Peking University First Hospital. The renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy examination. In addition, immunohistochemistry was used to detect the distribution of CD20+ B lymphocytes, CD3+ T lymphocytes and CD138+ plasma cells. Results A total of 24 patients were enrolled in the study, including 21 males (87.5%), 3 females (12.5%). The age was (58.0±10.8) years (38-75 years). Pathology analysis showed ectopic lymphoid-like structures were located in 16 (66.7%) cases and Russell bodies were detected in infiltrative plasma cells of 19(79.2%) cases with IgG4-TIN. Compared with cases without Russell body formation, cases with Russell body formation in renal interstitial plasma cells were more prone to show ectopic germinal center-like structure formation (P=0.001), tubular basement membrane (TBM) electron dense deposits (P=0.040) and reduced blood C3 levels (P=0.028). Conclusions Abnormal tubulointerstitial infiltration of ectopic lymphoid-like structures and plasma cells with prominent Russell body exist in IgG4-TIN patients, which suggests the persistent activation of lymphocytes and plasma cells in renal interstitium may contribute to the pathogenesis of IgG4-TIN.