Observed increases in CD4:CD8 and TIGIT expression during sofosbuvir-based therapy in a longitudinal hepatitis C cohort

Autor: Timothy J. Stevenson, Brian McMahon, Lisa Townshend-Bulson, Annette Hewitt, Youssef Barbour, Hannah Espera, Chriss Homan, Danielle Varney, Jim Gove, Wileina Rhodes, Mary Snowball, Evon Otto, Julia Plotnik, Susan Negus, Brenna Simons-Petrusa
Rok vydání: 2018
Předmět:
Zdroj: The Journal of Immunology. 200:166.4-166.4
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.200.supp.166.4
Popis: Chronic hepatitis C virus (HCV) infection reduces immune function through exhaustion and repertoire reduction. Sofosbuvir-based direct-acting antiviral (DAA) therapies offer >90% sustained virologic response (SVR) for HCV infection, but the extent of immune recovery and relationship with clinical factors are unknown. The longitudinal Alaska Hepatitis C Cohort provides an opportunity to evaluate immune recovery following sofosbuvir-based DAA and determine the influence of an extensive clinical and laboratory history. Forty-two persons (genotype 1; mean age 50 ± 12 years; 69% female) received 8 or 12-week sofosbuvir-based DAA therapy. Mean HCV RNA detection date was 2007 (range: 1994–2017). Pre-treatment HCV RNA levels averaged 4.9×106 IU/L (range: 4.9×104–2.4×107), were not detectable in any person after 4-weeks of therapy, and all achieved SVR. 18% (n=7) of persons had a fibrosis score of ≥F2 (moderate fibrosis to cirrhosis). Peripheral blood mononuclear cells (PBMCs) were evaluated at four time points: Pre-treatment (Pre), 4-weeks treatment (4wk), End of Treatment (EOT), and SVR post 12-weeks EOT (SVR-12) by flow cytometry to evaluate memory, exhaustion, and functional immune markers. Initial analysis revealed a significant increase in the CD4:CD8 from 4wk to EOT (p=0.007). Regulatory T-cells significantly increased at EOT and SVR-12 compared to 4wk (p=0.04 and 0.03, respectively). TIGIT showed a significant increasing trend in T-cells and NK cells throughout sampling timeline. Preliminary analysis indicates sofosbuvir-based DAA supports immune recovery to some extent. Additional analysis of immune recovery markers, determination of estimated date of HCV infection, and correlation of morbidity factors continues.
Databáze: OpenAIRE
Externí odkaz: