冷球蛋白血症性肾小球肾炎的透射电子显微镜 观察及临床病理特征

冷球蛋白血症性肾小球肾炎的透射电子显微镜 观察及临床病理特征

姚 瑶，孟庆阳，陆 敏*

(1.北京大学第三医院病理科，北京 100191；2.北京大学基础医学院病理学系，北京 100191)

摘 要 冷球蛋白血症是血循环中一种特殊类型的免疫球蛋白，常累及肾脏，在诊断冷球蛋白血症肾小球肾炎时，临床及血清学检查提供的诊断依据有限，透射电子显微镜观察可以协助确诊。本研究收集北京大学第三医院病理科诊断的冷球蛋白血症性肾小球肾炎肾活检组织10例，进行透射电子显微镜观察，结合常规的光镜检查、免疫荧光和免疫组织化学染色，总结冷球蛋白血症性肾小球肾炎的病理诊断要点。透射电子显微镜下观察到肾小球毛细血管内皮下大块高密度电子致密物沉积，其内见特殊结晶样物质，是诊断冷球蛋白血症肾小球肾炎的重要依据。冷球蛋白血症性肾小球肾炎的光镜特殊染色显示的双轨征、节段性白金耳和微血栓，免疫组织化学染色CD68阳性的单核-巨噬细胞浸润对诊断具有重要的提示作用。

关键词 冷球蛋白血症；肾脏疾病；透射电子显微镜；特殊结晶样物质

中图分类号 ：R692.6；Q336 文献标识码：A Doi:10.3969/j.issn.1000-6281.2025.02.008

Transmission electron microscopic observation and clinicopathological features of cryoglobulinemic glomerulonephritis

YAO Yao，MENG Qingyang，LU Min* ( 1. Department of Pathology, Third Hospital, Peking University, Beijing 100191; 2. Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People’s Republic of China，Beijing 100191,China)

Abstract Cryoglobulinemia is a unique type of immunoglobulin in the blood circulation, often affecting the kidney. In the diagnosis of cryoglobulinemic glomerulonephritis, clinical and serological examinations provide limited diagnostic basis, whereas transmission electron microscopy observation can assist in confirming the diagnosis. In this study, renal biopsy tissues from 10 cases of cryoglobulinemic glomerulonephritis diagnosed by the Department of Pathology, Peking University Third Hospital were analyzed. Transmission electron microscopy, immunofluorescence, and immunohistochemical staining were performed to summarize key pathological diagnostic features. Transmission electron microscopy revealed large, electron-dense deposits beneath the glomerular capillary endothelium, containing distinctive crystalloid structures, which serve as an important diagnostic hallmark of cryoglobulinemic glomerulonephritis. Light microscopy with special staining demonstrated characteristic features such as the double-track sign, segmental white ear, and microthrombus. Additionally, immunohistochemical staining highlighted CD68-positive monocyte-macrophage infiltration, playing a crucial role in the diagnosis process.

Keywords cryoglobulinemia; kidney disease; transmission electron microscopy; special crystalloid substances

[1] DESBOIS A C, CACOUB P, SAADOUN D. Cryoglobulinemia: An update in 2019 [J]. Joint Bone Spine, 2019, 86(6):707-713. [2] SILVAA F, PINTOA C, BARBOSAAA, et al. New insights in cryoglobulinemic vasculitis [J]. J Autoimmun, 2019, 105(12):102313-102320. [3] FUENTES A, MARDONES C, BURGOS P I. Understanding the cryoglobulinemias[J]. CurrRheumatol Rep, 2019, 21(11):60-70. [4] 王素霞,邹万忠,王盛兰,等. 冷球蛋白血症肾损害的超微结构特征及其诊断意义[J]. 电子显微学报,2005, 24(6):558-563. [5] SARGUR R, WHITE P, EGNER W. Cryoglobulin evaluation: Best practice?[J]. Am J ClinPathol, 2016, 145(6):789-795. [6 ] KOLOPP-SARDA M N, MIOSSEC P. Cryoglobulinemic vasculitis: Pathophysiological mechanisms and diagnosis[J]. CurrOpinRheumatol, 2021, 33(1):1-7. [7] SETHI S, DE VRIESE A S, FERVENZA F C. Acute glomerulonephritis[J]. Lancet, 2022, 399(10335): 1646-1663. [8] DAMOISEAUX J, TERVAERT J W C. Diagnostics and treatment of cryoglobulinaemia: It takes two to Tango [J]. Clin Rev Allergy Immunol, 2014 ,47(3):299-310. [9] DAVIDSON J S. Appropriate cryoglobulin investigations[J]. Ann Clin Biochem, 2010, 47(Pt5):491-496. [10] 邹万忠. 肾活检病理学[M].第5版. 北京：北京大学医学出版社，2021:346. [11] BEDDHU S, BASTACKY S, JOHNSON J P. The clinical and morphologic spectrum of renal cryoglobulinemia [J]. Medicine (Baltimore), 2002, 81(5):398–409. [12] ROCCATELLO D, FORNASIERI A, GIACHINO O, et al. Multicenter study on Hepatitis C Virus–related cryoglobulinemic glomerulonephritis [J]. Am J Kidney Dis, 2007, 49(1):69–82. [13] ROCCATELLO D, ISIDORO C, MAZZUCCO G, et al. Role of monocytes in cryoglobulinemia-associated nephritis [J]. Kidney Int, 1993, 43(5):1150–1155. [14] ROSENSTOCK J L, MARKOWITZ G S. Fibrillary Glomerulonephritis: An Update [J]. Kidney Int Rep, 2019,4(7):917-922. [15] INOTANI S, HORINO T, ISHIHARA M, et al. Immunotactoid glomerulopathy associated with monoclonal gammopathy[J]. Lancet, 2021, 397(10289):2081. [16] OJEMAKINDE K, TURBAT-HERRERA E A, ZENG X, et al. The many faces of cryoglobulinemic nephropathy: A clinico-pathologic study of 47 cases with emphasis on the value of electron microscopy[J]. Ultrastruct Pathol，2014，38(6):367–376. [17] LEUNG N, DROSOU M E, NASR S H. Dysproteinemias and glomerular disease [J]. Clin J Am Soc Nephrol, 2018, 13(1):128-139.