Sansonno Domenico, Tucci Felicia Anna, Troiani Laura, Lauletta Gianfranco, Montrone Michele, Conteduca Vincenza, Sansonno Loredana, Dammacco Franco
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
Blood. 2008 Sep 1;112(5):1620-7. doi: 10.1182/blood-2008-02-137455. Epub 2008 Jun 12.
Chemokine CXCL13, also known as BCA-1 (B cell-attracting chemokine-1) or BLC (B-lymphocyte chemoattractant), is a major regulator of B-cell trafficking. Hepatitis C virus (HCV) infection may be associated with B-cell dysfunction and lymphoproliferative disorders, including mixed cryoglobulinemia (MC). This study evaluates circulating levels of CXCL13 protein and specific mRNA expression in chronically HCV-infected patients with and without MC. Compared with healthy controls and HCV-infected patients without MC, CXCL13 serum levels were significantly higher in MC patients. The highest CXCL13 levels strongly correlated with active cutaneous vasculitis. CXCL13 gene expression in portal tracts, isolated from liver biopsy tissues with laser capture microdissection, showed enhanced levels of specific mRNA in MC patients with active cutaneous vasculitis. Specific CXCL13 gene mRNA expression was also up-regulated in skin tissue of these patients. These findings paralleled specific deposits of CXCL13 protein both in the liver and in the skin. Our results indicate that up-regulation of CXCL13 gene expression is a distinctive feature of HCV-infected patients. Higher levels of this chemokine in the liver as well as in the skin of patients with active MC vasculitis suggest a possible interrelation between these biologic compartments.
趋化因子CXCL13，也被称为BCA-1（B细胞趋化因子-1）或BLC（B淋巴细胞趋化剂），是B细胞迁移的主要调节因子。丙型肝炎病毒（HCV）感染可能与B细胞功能障碍和淋巴增殖性疾病有关，包括混合性冷球蛋白血症（MC）。本研究评估了患有和未患有MC的慢性HCV感染患者中CXCL13蛋白的循环水平和特定mRNA表达。与健康对照和未患有MC的HCV感染患者相比，MC患者的CXCL13血清水平显著更高。最高的CXCL13水平与活动性皮肤血管炎密切相关。通过激光捕获显微切割从肝活检组织中分离的门管区中，CXCL13基因表达显示，患有活动性皮肤血管炎的MC患者中特定mRNA水平升高。这些患者的皮肤组织中特定的CXCL13基因mRNA表达也上调。这些发现与肝脏和皮肤中CXCL13蛋白的特定沉积情况相符。我们的结果表明，CXCL13基因表达上调是HCV感染患者的一个显著特征。活动性MC血管炎患者肝脏和皮肤中这种趋化因子水平较高，提示这些生物区室之间可能存在相互关系。
