Análise de quimiocinas/citocinas séricas como biomarcadores de resposta terapêutica em Hepatite C Crônica e protótipo para monitorar imunoterapia de doenças infecciosas

Abstract

Background: The follow-up of biomarker changes triggered by cytokine-based therapy may provide relevant insights to subsidize the development and identification of predictors of therapeutic response. This study related serum chemokine/cytokine levels to the response to chronic hepatitis C treatment with the antiviral and imunomodulator drugs PEG-IFN and RBV. Methods: Longitudinal measurements of serum chemokine/cytokine levels were performed by cytometric-bead-array in patients with chronic hepatitis C, categorized according to virological response as non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. Results: Data demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-á, IFN-ã, along with decreased IL-10 levels in NR and increased levels of IL-6 and TNF in REL. SVR patients displayed lower baseline proinflammatory status with decreased CXCL8/IL-8, IL-12 and IL-17 levels. The inability to uphold IFN-á levels during treatment was characteristic of NR. The prominent baseline proinflammatory milieu observed in NR and REL patients yielded a restricted biomarker network, whereas SVR displayed a network with integrated cytokine connectivity. Noteworthy was that SVR presented a shift towards a proinflammatory pattern upon immunotherapy, assuming a pattern similar to that observed in NR and REL at baseline. Moreover, REC patients presented cytokines levels after or along treatment towards a profile similar to SVR at baseline. Analysis of baseline-fold changes during treatment pointed out IFN á and TNF as high-performance biomarkers to monitor immunotherapy outcome. Conclusion: The baseline proinflammatory status seems to predict non-response to PEG-IFN e RBV therapy in patients with chronic hepatitis C infected with HCV GT1. The ability to develop a proinflammatory profile during the treatment seems to predict SVR. The results highlight baseline IFNá and TNF as high performance biomarkers of SVR in GT1 infected patients treated by Peg-IFN and RBV. This knowledge may contribute for novel insights into the treatment and control of the continuous public health threat posed by the spreading/emerging viral infections.