乙型肝炎病毒通过驱动产生VH1-69编码抗体的先天性B细胞克隆扩增，导致混合性冷球蛋白血症。
Hepatitis B virus causes mixed cryoglobulinaemia by driving clonal expansion of innate B-cells producing a VH1-69-encoded antibody.
作者信息
Visentini Marcella, Pascolini Simona, Mitrevski Milica, Marrapodi Ramona, Del Padre Martina, Todi Laura, Camponeschi Alessandro, Axiotis Evangelos, Carlesimo Maurizio, De Santis Adriano, Fiorilli Massimo, Casato Milvia
机构信息
Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
Division of Gastroenterology and Hepatology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
出版信息
Clin Exp Rheumatol. 2016 May-Jun;34(3 Suppl 97):S28-32. Epub 2016 Jan 20.
OBJECTIVES
To investigate the expression of a VH1-69-encoded idiotype, and the phenotypic and functional features of monoclonal B-cells from patients with type II mixed cryoglobulinaemia (MC) secondary to chronic hepatitis B virus (HBV) infection.
METHODS
B-cell immunophenotype and expression of a VH1-69-encoded idiotype were investigated by flow cytometry. B-cell proliferative responses to stimuli were investigated by the CFSE dilution assay.
RESULTS
Two out of five patients with chronic HBV studied had massive monoclonal expansion of VH1-69-expressing B-cells. These cells had the peculiar CD21(low) phenotype and low responsiveness to stimuli typical of the VH1-69-expressing B-cells commonly expanded in MC secondary to hepatitis C virus (HCV) infection. In both patients, anti-HBV therapy led to the regression of MC and of VH1-69+ B-cell expansion.
CONCLUSIONS
VH1-69-encoded antibodies are known to preferentially recognise a variety of viral proteins including HCV E2, influenza A virus haemagglutinin and HIV gp41/gp120, and may serve as innate first line antiviral defense. Thus, like HCV, HBV may cause MC by protracted antigenic stimulation of VH1-69-expressing B-cells.
目的
研究慢性乙型肝炎病毒（HBV）感染所致II型混合性冷球蛋白血症（MC）患者中VH1 - 69编码独特型的表达情况，以及单克隆B细胞的表型和功能特征。
方法
采用流式细胞术研究B细胞免疫表型及VH1 - 69编码独特型的表达。通过羧基荧光素二乙酸琥珀酰亚胺酯（CFSE）稀释试验研究B细胞对刺激的增殖反应。
结果
在研究的5例慢性HBV患者中，有2例出现大量表达VH1 - 69的B细胞单克隆扩增。这些细胞具有特殊的CD21（低）表型，对刺激的反应性较低，这是丙型肝炎病毒（HCV）感染所致MC中常见的表达VH1 - 69的B细胞的典型特征。在这2例患者中，抗HBV治疗导致MC及VH1 - 69 + B细胞扩增消退。
结论
已知VH1 - 69编码的抗体优先识别多种病毒蛋白，包括HCV E2、甲型流感病毒血凝素和HIV gp41/gp120，并可能作为先天性一线抗病毒防御。因此，与HCV一样，HBV可能通过对表达VH1 - 69的B细胞的长期抗原刺激导致MC。
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