title: Interleukin 28B gene polymorphisms in hepatitis C virus-related cryoglobulinemic vasculitis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Domenico
authors.initials: D
authors.lastname: Sansonno
authors.forename: Sabino
authors.initials: S
authors.lastname: Russi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Serviddio
authors.forename: Vincenza
authors.initials: V
authors.lastname: Conteduca
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Loredana
authors.initials: L
authors.lastname: Sansonno
authors.forename: Fabio
authors.initials: F
authors.lastname: Pavone
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Lauletta
authors.forename: Maria Addolorata
authors.initials: MA
authors.lastname: Mariggiò
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
mesh_terms: D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use; D003449:Cryoglobulinemia / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D014657:Vasculitis / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: ANTIVIRAL THERAPIES; CRYOGLOBULINEMIC VASCULITIS; HCV INFECTION; INTERLEUKIN 28B; SINGLE-NUCLEOTIDE POLYMORPHISM