白细胞介素 28B 基因多态性与丙型肝炎病毒相关性冷球蛋白血症性血管炎。

Interleukin 28B gene polymorphisms in hepatitis C virus-related cryoglobulinemic vasculitis.

机构信息

From the Section of Internal Medicine and Clinical Oncology, Laboratory of General Pathology and Experimental Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari; Section of Internal Medicine, Department of Medical Sciences, and Section of Medical Genetics, Department of Biomedical Sciences, University of Foggia, Foggia, Italy.

出版信息

J Rheumatol. 2014 Jan;41(1):91-8. doi: 10.3899/jrheum.130527. Epub 2013 Dec 1.

DOI:10.3899/jrheum.130527

PMID:24293567

Abstract

OBJECTIVE

Single-nucleotide polymorphisms (SNP) in the interleukin 28B (IL-28B) gene region are strongly predictive of the response of infected patients to antiviral therapy for hepatitis C virus (HCV). We sought to determine the prevalence of SNP IL-28B rs12979860 C/C and non-C/C (C/T plus T/T) genotypes in HCV-related cryoglobulinemic vasculitis (CV), as compared with HCV-positive patients without CV. We also searched for their association with peculiar clinical manifestations of CV and potential influence on the complete response (virological, molecular, and immunological) to the therapy.

METHODS

The study cohort comprised 159 and 172 HCV-infected patients with and without CV, respectively, prospectively followed starting from 1990. SNP rs12979860 genotyping was performed by Taq-Man allelic discrimination. In 106 patients (66.6%) with CV, the profile of circulating B cell clonalities was determined as well. All patients with CV were treated with pegylated interferon-α/ribavirin-based antiviral therapy.

RESULTS

The T/T IL-28B genotype was more common in patients with CV than in those without (17% vs 8.1%, p = 0.02). In patients with CV, compared with non-C/C variants, the IL-28B C/C genotype was associated with a higher rate of complete response (52.6% vs 39.2%, p = 0.13), whereas a treatment response of 61.4% was demonstrated when solely virological response was considered (p = 0.008). A higher frequency of expanded B cell clonalities in the circulation (84.2% vs 55.9%; p = 0.005), kidney involvement (21% vs 2.9%; p = 0.003), and B cell non-Hodgkin lymphoma (17.5% vs 6.8%; p = 0.048), were also observed.

CONCLUSION

In HCV-positive patients with CV, the IL-28B C/C genotype is distinguished biologically by a higher frequency of restriction of B cell response and clinically by a higher risk of cryoglobulinemic nephropathy and B cell malignancies, while acting as an independent predictor of a sustained virological response to antiviral therapy. In addition, we found that IL-28B T/T variant was more prevalent in patients with CV than in those without.

摘要

目的

白细胞介素 28B（IL-28B）基因区域的单核苷酸多态性（SNP）强烈预测感染患者对丙型肝炎病毒（HCV）抗病毒治疗的反应。我们试图确定 SNP IL-28B rs12979860 C/C 和非-C/C（C/T 加 T/T）基因型在丙型肝炎相关冷球蛋白血症性血管炎（CV）中的患病率，与无 CV 的 HCV 阳性患者相比。我们还寻找了它们与 CV 特殊临床表现的关联，以及对治疗的完全反应（病毒学、分子和免疫学）的潜在影响。

方法

研究队列包括 159 名和 172 名分别前瞻性随访的 HCV 感染患者，分别患有和不患有 CV。通过 Taq-Man 等位基因鉴别法对 SNP rs12979860 进行基因分型。在 106 名（66.6%）患有 CV 的患者中，还确定了循环 B 细胞克隆的特征。所有患有 CV 的患者均接受聚乙二醇干扰素-α/利巴韦林为基础的抗病毒治疗。

结果

与无 CV 的患者相比，CV 患者的 T/T IL-28B 基因型更为常见（17%比 8.1%，p=0.02）。与非-C/C 变体相比，在患有 CV 的患者中，IL-28B C/C 基因型与更高的完全反应率相关（52.6%比 39.2%，p=0.13），而当仅考虑病毒学反应时，显示出 61.4%的治疗反应（p=0.008）。在循环中也观察到更高频率的扩展 B 细胞克隆（84.2%比 55.9%；p=0.005）、肾脏受累（21%比 2.9%；p=0.003）和 B 细胞非霍奇金淋巴瘤（17.5%比 6.8%；p=0.048）。

结论

在患有 CV 的 HCV 阳性患者中，IL-28B C/C 基因型在生物学上表现为 B 细胞反应受限的频率更高，在临床上表现为冷球蛋白血症性肾病和 B 细胞恶性肿瘤的风险更高，同时作为抗病毒治疗持续病毒学反应的独立预测因子。此外，我们发现 IL-28B T/T 变体在患有 CV 的患者中比在没有 CV 的患者中更为普遍。