Sansonno Domenico, Tucci Felicia Anna, Ghebrehiwet Berhane, Lauletta Gianfranco, Peerschke Ellinor I B, Conteduca Vincenza, Russi Sabino, Gatti Pietro, Sansonno Loredana, Dammacco Franco
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Italy.
J Immunol. 2009 Nov 1;183(9):6013-20. doi: 10.4049/jimmunol.0902038. Epub 2009 Oct 14.
Mixed cryoglobulinemia (MC) is a lymphoproliferative disorder observed in approximately 10 to 15% of hepatitis C virus (HCV)-infected patients. Circulating, nonenveloped HCV core protein, which has been detected in cryoprecipitable immune complexes, interacts with immunocytes through the receptor for the globular domain of C1q protein (gC1q-R). In this study, we have evaluated circulating gC1q-R levels in chronically HCV-infected patients, with and without MC. These levels were significantly higher in MC patients than in those without MC and in healthy controls and paralleled specific mRNA expression in PBL. Soluble gC1q-R circulates as a complexed form containing both C1q and HCV core proteins. Higher serum gC1q-R levels negatively correlated with circulating concentrations of the C4d fragment. The presence of sequestered C4d in the vascular bed of skin biopsies from MC patients was indicative of in situ complement activation. In vitro studies showed that release of soluble gC1q-R is regulated by HCV core-mediated inhibition of cell proliferation. Our results indicate that up-regulation of gC1q-R expression is a distinctive feature of MC, and that dysregulated shedding of C1q-R molecules contributes to vascular cryoglobulin-induced damage via the classic complement-mediated pathway.
混合性冷球蛋白血症（MC）是一种在约10%至15%的丙型肝炎病毒（HCV）感染患者中观察到的淋巴增殖性疾病。在可冷沉淀的免疫复合物中检测到的循环性、无包膜HCV核心蛋白，通过C1q蛋白球状结构域受体（gC1q-R）与免疫细胞相互作用。在本研究中，我们评估了慢性HCV感染患者（有或无MC）的循环gC1q-R水平。这些水平在MC患者中显著高于无MC患者和健康对照，并且与外周血淋巴细胞（PBL）中的特定mRNA表达平行。可溶性gC1q-R以包含C1q和HCV核心蛋白的复合形式循环。血清gC1q-R水平较高与C4d片段的循环浓度呈负相关。MC患者皮肤活检血管床中存在隔离的C4d表明存在原位补体激活。体外研究表明，可溶性gC1q-R的释放受HCV核心介导的细胞增殖抑制调节。我们的结果表明，gC1q-R表达上调是MC的一个独特特征，并且C1q-R分子的失调脱落通过经典补体介导途径导致血管冷球蛋白诱导的损伤。
