两名中国患者的纤维蛋白原Aα链淀粉样变性
Fibrinogen A Alpha-Chain Amyloidosis in Two Chinese Patients.
作者信息
Li Zhen-Yu, Wang Shuang, Li Dan-Yang, Liu Dan, Wang Su-Xia, Yu Xiao-Juan, Liu Gang, Zhou Fu-De, Zhao Ming-Hui
机构信息
Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, Beijing, China.
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
出版信息
Front Med (Lausanne). 2022 Apr 28;9:869409. doi: 10.3389/fmed.2022.869409. eCollection 2022.
OBJECTIVES
Fibrinogen A alpha-chain amyloidosis (AFib amyloidosis) is the most common form of hereditary renal amyloidosis in the United Kingdom and Europe, but has rarely been reported in Asia. In this study, we reported two AFib amyloidosis patients in China, reviewing the literature and summarizing main characteristics of AFib amyloidosis in Asia.
METHODS
Two unrelated Chinese patients were diagnosed with AFib amyloidosis by clinical presentation, renal biopsy, mass spectrometry and DNA sequencing in Peking University First Hospital of China from 2014 to 2016.
RESULTS
Both of the patients presented with proteinuria, edema and hypertension. Renal biopsies of two patients showed extensive amyloid deposits (Congo red positive) in glomeruli, and focal tubulointerstitial amyloid deposits was also found in patient 1. Besides, hepatic involvement of amyloidosis has been detected by liver biopsy in patient 1. By electron microscopy, randomly arranged fibrils in a diameter of 8-12 nm was identified in mesangial matrix and subendothelial area of glomeruli. Immunohistochemistry demonstrated amyloid deposits were strongly positive for fibrinogen Aα in glomeruli and positive for LECT2 in the interstitium of renal medulla and the liver in Patient 1. Unevenly positive staining for both fibrinogen Aα and ApoA-I were found in Patient 2. Fibrinogen Aα was the most abundant amyloidogenic protein in both patients identified by laser microdissection and mass spectrometry-based proteomic analysis. Genetic analysis revealed the gene () mutation in both patients, including a new deletion mutation [c.1639delA (p.Arg547Glyfs21; NM_000508)] in Patient 2. Genetic analysis of the gene in patient 1 revealed a codon change from ATC to GTC at position 172 [c.172A>G (p.Ile58Val; NM_002302)], which is a common polymorphism (SNP rs31517) in all ALECT2 amyloidosis patients.
CONCLUSIONS
We reported two AFib amyloidosis patients in China, one of them coexisted with ALECT2 amyloidosis simultaneously.
目的
纤维蛋白原Aα链淀粉样变性（AFib淀粉样变性）是英国和欧洲遗传性肾淀粉样变性最常见的形式，但在亚洲鲜有报道。在本研究中，我们报告了中国的两例AFib淀粉样变性患者，回顾相关文献并总结亚洲AFib淀粉样变性的主要特征。
方法
2014年至2016年，在中国北京大学第一医院，通过临床表现、肾活检、质谱分析和DNA测序，确诊了两名无血缘关系的中国患者患有AFib淀粉样变性。
结果
两名患者均表现为蛋白尿、水肿和高血压。两名患者的肾活检显示肾小球有广泛的淀粉样沉积（刚果红阳性），患者1还发现局灶性肾小管间质淀粉样沉积。此外，患者1经肝活检检测到淀粉样变性累及肝脏。电镜检查在肾小球系膜基质和内皮下区域发现直径8 - 12nm的随机排列的原纤维。免疫组化显示，患者1肾小球内淀粉样沉积对纤维蛋白原Aα呈强阳性，肾髓质间质和肝脏对LECT2呈阳性。患者2对纤维蛋白原Aα和载脂蛋白A - I均呈不均匀阳性染色。通过激光显微切割和基于质谱的蛋白质组学分析确定，纤维蛋白原Aα是两名患者中最丰富的淀粉样蛋白生成蛋白。基因分析显示两名患者均存在 基因（）突变，其中患者2有一个新的缺失突变[c.1639delA（p.Arg547Glyfs21；NM_000508）]。对患者1的 基因进行基因分析发现，第172位密码子从ATC变为GTC [c.172A>G（p.Ile58Val；NM_002302）]，这是所有ALECT2淀粉样变性患者中常见的多态性（单核苷酸多态性rs31517）。
结论
我们报告了中国的两例AFib淀粉样变性患者，其中一例同时合并ALECT2淀粉样变性。
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