Impact of Soluble CD26 on Treatment Outcome and Hepatitis C Virus-Specific T Cells in Chronic Hepatitis C Virus Genotype 1 InfectionReportar como inadecuado




Impact of Soluble CD26 on Treatment Outcome and Hepatitis C Virus-Specific T Cells in Chronic Hepatitis C Virus Genotype 1 Infection - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

Interferon and ribavirin therapy for chronic hepatitis C virus HCV infection yields sustained virological response SVR rates of 50–80%. Several factors such as non-1 genotype, beneficial IL28B genetic variants, low baseline IP-10, and the functionality of HCV-specific T cells predict SVR. With the pending introduction of new therapies for HCV entailing very rapid clearance of plasma HCV RNA, the importance of baseline biomarkers likely will increase in order to tailor therapy. CD26 DPPIV truncates the chemokine IP-10 into a shorter antagonistic form, and this truncation of IP-10 has been suggested to influence treatment outcome in patients with chronic HCV infection patients. In addition, previous reports have shown CD26 to be a co-stimulator for T cells. The aim of the present study was to assess the utility of CD26 as a biomarker for treatment outcome in chronic hepatitis C and to define its association with HCV-specific T cells.

Methods

Baseline plasma from 153 genotype 1 and 58 genotype 2-3 infected patients enrolled in an international multicenter phase III trial DITTO-HCV and 36 genotype 1 infected patients participating in a Swedish trial TTG1 were evaluated regarding baseline soluble CD26 sCD26 and the functionality of HCV-specific CD8+ T cells.

Results

Genotype 1 infected patients achieving SVR in the DITTO P = 0.002 and the TTG1 P = 0.02 studies had lower pretreatment sCD26 concentrations compared with non-SVR patients. Sixty-five percent of patients with sCD26 concentrations below 600 ng-mL achieved SVR compared with 39% of the patients with sCD26 exceeding 600 ng-mL P = 0.01. Patients with sCD26 concentrations below 600 ng-mL had significantly higher frequencies of HCV-specific CD8+ T cells P = 0.02.

Conclusions

Low baseline systemic concentrations of sCD26 predict favorable treatment outcome in chronic HCV infection and may be associated with higher blood counts of HCV-specific CD8+ T cells.



Autor: Jonas Söderholm , Jesper Waldenström , Galia Askarieh, Massimo Pilli, Pierre-Yves Bochud, Francesco Negro, Jean-Michel Pawlotsk

Fuente: http://plos.srce.hr/



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