ST114 IL28B SNP does not predict the outcome of Hepatitis C Virus-specific cellular immune response

Abstract

The CC genotype of single nucleotide polymorphism (SNP) at the rs12979860 site of interleukin (IL)28B gene has been associated with spontaneous Hepatitis C Virus (HCV) clearance and interferon-treatment response. The role of IL28B SNP in predicting HCV-specific cell mediated immune (CMI) responses has not been investigated. We recently reported HCV-specific CMI responses in exposed uninfected healthcare workers (HCW) at high risk of infection without detecting viremia or seroconversion. The HCW at the National Liver Institute serve a patient cohort with ∼90% HCV prevalence. We investigated the HCV-specific CMI response in seronegative, aviremic HCW (n=102) and their chronic (n=36) and resolved (n=20) counterparts. We used an enzyme-linked immunospot (ELISPOT) assay to quantify interferon gamma production in response to a set of genotype 4a overlapping 15mer peptide pools covering the whole HCV genome. Also, we examined IL28B genotype of these HCW by real-time PCR. We confirmed our previous findings of HCV-specific CMI without viremia or seroconversion in more than 20% of these HCW suggesting clearance of low levels of HCV exposures. The percentage of IL28B CC allele in chronic, resolved and seronegative aviremic subjects were 31%, 45%, and 46%, while that of the TT allele was 31%, 0% and 8%, respectively. Although IL28B SNP predicted the outcome of HCV infection, we did not find any correlation between the different IL28B genotypes and the outcome of HCV-specific CMI responses in the three groups tested (p>0.05). Taken together, these data support the notion that a protective HCV vaccine targeting CMI is feasible regardless of IL28B genotype. Also, IL28B does not predict the outcome of HCV-specific CMI responses.