title: Impact of soluble CD26 on treatment outcome and hepatitis C virus-specific T cells in chronic hepatitis C virus genotype 1 infection.
abstract: 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.
authors: Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden. jonas.soderholm@gmail.com
authors: Jonas
authors: J
authors: Söderholm
authors: Jesper
authors: J
authors: Waldenström
authors: Galia
authors: G
authors: Askarieh
authors: Massimo
authors: M
authors: Pilli
authors: Pierre-Yves
authors: PY
authors: Bochud
authors: Francesco
authors: F
authors: Negro
authors: Jean-Michel
authors: JM
authors: Pawlotsky
authors: Stefan
authors: S
authors: Zeuzem
authors: Carlo
authors: C
authors: Ferrari
authors: Gunnar
authors: G
authors: Norkrans
authors: Rune
authors: R
authors: Wejstål
authors: Johan
authors: J
authors: Westin
authors: Avidan U
authors: AU
authors: Neumann
authors: Bart L
authors: BL
authors: Haagmans
authors: Magnus
authors: M
authors: Lindh
authors: Gabriele
authors: G
authors: Missale
authors: Kristoffer
authors: K
authors: Hellstrand
authors: Martin
authors: M
authors: Lagging
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012372:ROC Curve; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D018819:Dipeptidyl Peptidase 4