Natural killer cell dynamic profile is associated with treatment outcome in patients with chronic HCV infection

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• 作者：Barbara Oliviero¹ ; Dalila Mele¹ ; Elisabetta Degasperi⁴ ; Alessio Aghemo⁴ ; Eleonora Cremonesi¹ ; Maria Grazia Rumi⁵ ; Carmine Tinelli² ; Stefania Varchetta¹ ; Stefania Mantovani¹ ; Massimo Colombo⁴ ; Mario U. Mondelli¹ ; ³ ; ^{mario.mondelli@unipv.it}
• 关键词：NK ; natural killer ; HCV ; hepatitis C virus ; IFN¦Ã ; interferon gamma ; TNF¦Á ; tumour necrosis factor alpha ; DAAs ; directly-acting antiviral ; PegIFN¦Á ; pegylated interferon alpha ; RBV ; ribavirin ; SOC ; standard of care ; SVR ; sustained virological response ; NR
• 刊名：Journal of Hepatology
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：59
• 期：1
• 页码：38-44
• 全文大小：620 K

文摘

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Background & Aims

A substantial proportion of patients with chronic hepatitis C virus infection treated with pegylated interferon ¦Á/ribavirin fail to achieve sustained virological response (SVR). Since growing evidence suggests that innate immunity may influence treatment responses, we examined natural killer (NK) cell phenotypic and functional changes during standard antiviral therapy.

Methods

Expression of several NK-cell regulatory molecules was evaluated by flow cytometry in 37 consecutive patients with chronic HCV infection at baseline and at different time points during and after discontinuation of treatment. Cytokine production was evaluated by intracellular staining. Cytolytic potential was assessed as degranulation and as antibody-dependent cytotoxicity.

Results

Baseline frequencies of CD56^dim NK cells and perforin content were significantly higher, whereas CD16 expression was lower in SVR vs. non-responder subjects. Analysis by linear regression for repeated measures during the first 12 weeks showed significantly increased frequencies of activated (CD69⁺) NK cells in rapid virological responders (RVR) and identified a typical NK cell profile associated with SVR, featuring higher NK perforin content, lower CD16 expression, and higher proportion of CD56^dim/CD16^? cells. Moreover, SVR patients displayed higher natural and antibody-dependent NK cell cytotoxicity. IL28B rs12979860 CC homozygosis was significantly associated with SVR, independently of NK-cell phenotype and function.

Conclusions

Different NK-cell phenotypic and functional features, in patients with chronic hepatitis C treated with standard therapy, were observed between non-responder vs. SVR patients, suggesting a potential role of NK cells in the response to treatment.