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Viral hepatitis
PMO-158 RS12979860 CC genotype is associated with baseline high numbers of CD56bright NK-cells, low numbers of CD3-CD56-CD16+ cells, low IL-10 HCV-specific production in CH-C therapy responders
  1. I Carey,
  2. M J Bruce,
  3. D Joshi,
  4. D Vergani,
  5. K Agarwal
  1. Institute of Liver Studies and Transplantation, King's College Hospital, London, UK

Abstract

Introduction IL28B gene single nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 help to predict treatment response in chronic hepatitis C (CH-C). Strong immune responses control HCV infection. Little is known on the association between IL28B SNPs, innate/adaptive immune responses in relation to Peg-IFN/ribavirin sustained virologic response (SVR) in CH-C.

Aims To evaluate the relationship between rs12979860 and rs8099917, pre-treatment frequency/phenotype of natural killer (NK) cells (innate immunity), HCV-specific immune responses (adaptive immunity), and SVR.

Patients 35 CH-C genotype 1 patients (23 males, median age 37 years) treated with Peg-IFN/ribavirin were divided in two groups: 18 responders (SVR), 17 non-SVR (nine non-responders and eight relapsers).

Methods rs12979860 and rs8099917 were tested by direct sequencing. Baseline numbers of NK cells (CD3CD56+), their subsets CD56dim/CD56bright, CD3CD56±CD16±, and expression of NK cells activation/inhibition (NKG2D/NKG2A) markers were investigated by flowcytometry on peripheral blood mononuclear cells (PBMC). PBMC IFN-γ/IL-10 production after exposure to HCV antigens was evaluated by intracellular cytokine staining. Results are presented as medians.

Results Rs12979860 genotype CC was more frequent in SVR than non-SVR (85% vs 15%), while non-CC genotypes (CT/TT) were present in 32% SVR vs 68% non-SVR. 75% SVR had TT genotype for rs 8099917 vs 25% non-SVR and non-TT genotypes (GT/GG) were more frequent in non-SVR then SVR (80% vs 20%, all pbright subset was higher in SVR than non-SVR (6.4% vs 2.9%, p=0.03). CD3CD56CD16+ cells subset was more frequent in non-SVR than SVR (11.4% vs 8.6%, p=0.05). The proportion of CD56dim+/NKG2D+ cells was higher in SVR than non-SVR (47.1% vs 36.3%, p=0.04). While number of CD4+ HCV core-specific IFN-γ producing cells was similar in all groups, the frequency of HCV core-specific CD4+ cells producing IL-10 was higher in non-SVR than SVR (4.3% vs 1.8%, p=0.05). Comparing patients according to rs12979860 CC vs no CC genotypes, CC genotype patients had more CD56bright cells (6.6% vs 3.1%, p=0.04), fewer CD3CD56CD16+ NK cells (8.7% vs 11.1%, p=0.05) and fewer HCV-core specific CD4+/IL-10+ cells (1.9% vs 4.2%, p=0.05). There were no associations between rs8099917 genotypes TT vs no TT and innate or adaptive immune responses in this cohort.

Conclusion High numbers of CD56bright NK cells, low numbers of unconventional CD3CD56CD16+ NK cells, and low HCV-specific IL-10 production at baseline are associated with IL28B gene SNP rs12979860 CC genotype and successful antiviral treatment of CH-C genotype 1.

Competing interests None declared.

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