DNAJ热休克蛋白家族成员B9阳性纤维样肾小球病的临床病理特征分析  

Clinicopathological analysis of DNAJ heat shock protein family member B9-positive fibrillary glomerulonephritis

作　　者：张鑫[1] 雍自昊 喻小娟[1] 王素霞[1,3] 周福德[1] 赵明辉[1] Zhang Xin;Yong Zihao;Yu Xiaojuan;Wang Suxia;Zhou Fude;Zhao Minghui(Renal Division,Peking University First Hospital Institute of Nephrology,Peking University Key Laboratory of Renal Disease,Ministry of Health of China Key Laboratory of Chronic Kidney Disease Prevention and Treatment,Ministry of Education of China Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases,Chinese Academy of Medical Sciences,Beijing 100085,China;Center for Life Sciences,Peking University,Beijing 100084,China;Laboratory of Electron Microscopy,Pathological Center,Peking University First Hospital,Beijing 100085,China)

机构地区：[1]北京大学第一医院肾内科,北京大学肾脏疾病研究所,卫生部肾脏疾病重点实验室慢性肾脏病防治教育部重点实验室(北京大学),中国医学科学院免疫介导肾病诊治创新单元,北京100085 [2]北京大学生命科学联合中心,北京100084 [3]北京大学第一医院电镜室,北京100085

出　　处：《中华肾脏病杂志》2022年第3期161-167,共7页Chinese Journal of Nephrology

基　　金：国家自然科学基金(82070747);中国医学科学院医学与健康科技创新工程项目(2019-I2M-5-046)。

摘　　要：目的总结和分析DNAJ热休克蛋白家族成员B9(DNAJ heat shock protein family member B9, DNAJB9)阳性的纤维样肾小球病(fibrillary glomerulonephritis, FGN)患者临床病理改变的特征。方法回顾性分析2011年1月至2021年1月在北京大学第一医院肾内科诊断的5例DNAJB9阳性FGN患者的临床及病理资料, 总结其临床病理改变特征。结果 5例FGN患者入选本研究, 性别比为4∶1(女∶男), 中位年龄29岁(24~71岁);临床表现为肾病综合征2例, 蛋白尿3例;1例肉眼血尿, 4例轻度镜下血尿。5例患者均无单克隆免疫球蛋白血症证据。FGN肾脏病理表现多样, 光镜下可表现为系膜增生性、系膜结节状硬化、膜增生性、不典型膜性肾病样改变, 可伴有新月体形成;免疫荧光以IgG和C3在系膜区和毛细血管壁云雾颗粒样、条带样沉积为主, IgG亚型以IgG1和IgG4为主;电镜下可见直径8~30 nm纤维样物质, 主要沉积于系膜区和内皮下, 可伴有基底膜内沉积, 少见上皮下沉积。FGN患者肾脏预后不佳, 2例起病时表现为肾病综合征的患者中, 1例患者于起病1周内进展至终末期肾病, 1例患者经积极免疫抑制剂治疗后1年内进展至终末期肾病;3例起病时尿蛋白量<3 g/24 h的患者, 经肾素-血管紧张素系统阻滞剂治疗后, 2例蛋白尿缓解, 1例尿蛋白量轻度升高, 肾功能均维持稳定。结论中国FGN患者以青年起病多见, 临床主要表现为蛋白尿、微量镜下血尿。FGN诊断依赖电镜下发现系膜区、内皮下直径约10~30 nm纤维样物质, DNAJB9蛋白免疫组化检测阳性可作为确诊FGN的重要标志物。FGN患者肾脏预后较差, 目前尚无有效的针对性治疗方案。Objective To summarize and analyze the clinicopathological characteristics of patients with DNAJ heat shock protein family member B9(DNAJB9)-positive fibrillary glomerulonephritis(FGN).Methods The clinical and pathological data of 5 patients with DNAJB9-positive FGN diagnosed in Peking University First Hospital from January 2011 to January 2021 were retrospectively collected and analyzed.Results Among the 5 patients,the female to male ratio was 4∶1,and the median age was 29 years old(24-71 years old).The clinical manifestations included 2 cases with nephrotic syndrome and 3 cases with proteinuria.One patient had gross hematuria,and 4 cases had mild microscopic hematuria.None of the 5 patients had evidence of monoclonal gammopathy.The renal pathological pattern of FGN showed mesangial-proliferative glomerulonephritis,mesangial nodular sclerosis,membranoproliferative glomerulonephritis,and atypical membranous nephropathy.Crescents formation could be accompanied.Immunofluorescence staining showed smudgy and granular IgG and C3 deposition in the mesangial region and capillary wall,and the subtypes of IgG were mainly IgG1 and IgG4.Under electron microscopy,fibrillary deposits with a diameter of 8-30 nm were observed in the mesangial and subendothelial area,accompanied by deposition in basement membrane and occasionally subepithelial area.The renal prognosis of FGN patients was poor.One patient entered end-stage renal disease within one week,and another patient entered end-stage renal disease within one year despite immunosuppressant therapy in 2 cases with nephrotic syndrome at onset.One patient had worsening proteinuria despite renin-angiotensin system(RAS)blocker treatment.Two patients achieved complete renal remission and stable renal function after RAS blocker treatment.Conclusions Most FGN patients in China are young people.The main clinical manifestations are proteinuria or mild microscopic hematuria.The diagnosis depends on the discovery of fibrillary deposits in the mesangial area and subendothelial area wit

关 键 词：肾小球肾炎 病理学 临床 热休克蛋白质类 纤维样肾小球病 DNAJ热休克蛋白家族成员B9 

分 类 号：R692.6[医药卫生—泌尿科学]