Expression patterns of immune checkpoint proteins and -induced cytokines in chronic hepatitis B virus-infected and uninfected individuals: A cross-sectional study.

BACKGROUND AND AIM

Chronic hepatitis B virus (CHB) infection remains a major public health problem. The American Association for the Study of Liver Diseases (AASLD) 2018 Hepatitis B Guidelines provide that CHB individuals not requiring antiviral therapy yet are monitored to determine the need for antiviral therapy in the future; however, these tests do not include measurement of cytokines and immune cell characterization. This case-control study compared the cytokine and immune checkpoint protein expression profiles between CHB individuals not yet on antiviral treatment and hepatitis B virus (HBV)-negative individuals.

METHODS

CD4 and CD8 T cells from CHB and HBV-negative individuals were characterized for immune checkpoint proteins programmed cell death-1 (PD1), T cell Immunoglobulin domain and mucin domain-containing protein 3 (TIM-3), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) (CD152), and a memory marker CXCR3 (CD183) using flow cytometry. Malaria-induced cytokine expression levels were determined by stimulating their blood cells with 3D7 strain antigens (CSP, AMA-1, and TRAP) in whole blood assays, and cytokine levels were measured using a 13-plex Luminex kit.

RESULTS

HBV-negative and CHB individuals had comparable levels of CD4+ and CD8+ T cells. However, a proportion of the CD4+ and CD8+ populations from both groups, which were CXCR3+, expressed PD-1 and CD152. The ability to produce cytokines in response to malaria antigen stimulation was not significantly different between the groups.

CONCLUSION

These findings support excluding CHB individuals from antiviral therapy at this stage of infection. However, CHB individuals require regular monitoring to determine the need for later antiviral treatment.