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Programmed cell death-1 is involved with peripheral blood immune cell profiles in patients with hepatitis C virus antiviral therapy.

Authors :
Miura, Miyabi
Nishino, Michiko
Kawaguchi, Kazunori
Li, Shihui
Shimakami, Tetsuro
Tamai, Toshikatsu
Nakagawa, Hidetoshi
Terashima, Takeshi
Iida, Noriho
Takatori, Hajime
Arai, Kuniaki
Sakai, Yoshio
Yamashita, Tatsuya
Honda, Masao
Kaneko, Shuichi
Mizukoshi, Eishiro
Yamashita, Taro
Source :
PLoS ONE; 5/23/2024, Vol. 19 Issue 5, p1-16, 16p
Publication Year :
2024

Abstract

Mutations in the non-structural protein regions of hepatitis C virus (HCV) are a cause of a non-sustained virological response (SVR) to treatment with direct-acting antivirals (DAAs) for chronic hepatitis; however, there are non-SVR cases without these mutations. In this study, we examined immune cell profiles in peripheral blood before and after ombitasvir/paritaprevir/ritonavir treatment and screened for genes that could be used to predict the therapeutic effects of DAAs. Fluorescence-activated cell sorting analysis indicated that the median frequencies of programmed cell death-1-positive (PD-1+) effector regulatory T cells (eTregs), PD-1+CD8+ T cells, and PD-1+Helper T cells were decreased significantly in SVR cases, but without significant changes in non-SVR cases. The frequency of PD-1+ naïve Tregs was significantly higher in the SVR group than in the non-SVR group before and after treatment. Similar results were found in patients treated with other DAAs (e.g., daclatasvir plus asunaprevir) and supported an immune response after HCV therapy. RNA-sequencing analysis indicated a significant increase in the expression of genes associated with the immune response in the SVR group, while genes related to intracellular and extracellular signal transduction were highly expressed in the non-SVR group. Therefore, we searched for genes associated with PD-1+ eTregs and CD8+ T cells that were significantly different between the SVR and non-SVR groups and found that T-box transcription factor 21 was associated with the non-SVR state. These results indicate that PD-1-related signaling pathways are associated with a non-SVR mechanism after DAAs treatment separate from mutation-related drug resistance. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19326203
Volume :
19
Issue :
5
Database :
Complementary Index
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
177420619
Full Text :
https://doi.org/10.1371/journal.pone.0299424