title: Therapy with interferon-alpha and ribavirin for chronic hepatitis C virus infection upregulates membrane HLA-ABC, CD86, and CD28 on peripheral blood mononuclear cells.
abstract: Multiple interferon-stimulated genes (ISGs) involving T-cell activation are upregulated during initial interferon-alpha-based therapy for chronic hepatitis C virus (HCV) infection. However, the long-term impact on therapeutic outcome in patients remains unknown. In this study, the effects of anti-HCV therapy on the surface expression of HLA-ABC, CD86, and CD28 were longitudinally assessed. These proteins are integral membrane receptors of antigen presentation and triggering of costimulatory signals for activating CD8+ T cells. Peripheral blood mononuclear cells were collected at baseline and post-treatment for 1 day, and 2, 4, 12, and 24 weeks, respectively. This treatment led to a time-related elevation of membrane levels of HLA-ABC and CD86 on B-cells and monocytes in patients with a sustained response (n = 23), but not in those without (n = 8). Meanwhile, upregulation of CD28 on CD4+ and CD8+ T cells was comparable in both groups of sustained responders and non-responders. Steady increases in the B cells' surface and intracellular HLA-ABC were observed, thus, the surface-to-intracellular ratios did not alter over the period of treatment. Furthermore, multivariate analysis shows that increased HLA-ABC on monocytes by week 12 correlates significantly with sustained response (P = 0.033). In conclusion, differential modulation of T-cell activation ISGs, such as HLA-ABC and CD86 might correlate with the outcome of interferon-alpha-based therapy in chronic hepatitis C patients.
authors.affiliation: Department of Internal Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Pin-Nan
authors.initials: PN
authors.lastname: Cheng
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Wei
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
authors.forename: Jiann-Shiuh
authors.initials: JS
authors.lastname: Chen
authors.forename: Kung-Chia
authors.initials: KC
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000954:Antigens, Surface; D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin