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

Artikel i vetenskaplig tidskrift
Författare Jonas Söderholm
Jesper Waldenström
Galia Askarieh
M. Pilli
P. Y. Bochud
F. Negro
J. M. Pawlotsky
S. Zeuzem
C. Ferrari
Gunnar Norkrans
Rune Wejstål
Johan Westin
A. U. Neumann
B. L. Haagmans
Magnus Lindh
G. Missale
Kristoffer Hellstrand
Martin Lagging
Publicerad i PLoS ONE
Volym 8
Nummer/häfte 2
ISSN 1932-6203
Publiceringsår 2013
Publicerad vid Institutionen för biomedicin, avdelningen för infektionssjukdomar
Språk en
Länkar dx.doi.org/10.1371/journal.pone.005...
https://gup.ub.gu.se/file/110538
Ämnesord interferon-gamma, inducible protein-10, ribavirin therapy, antiviral, therapy, genetic-variation, viral clearance, hcv infection, association, predicts, il28b
Ämneskategorier Infektionsmedicin

Sammanfattning

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.

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