Single cell profiling of functionally cured Chronic Hepatitis B patients reveals the emergence of activated innate and an altered adaptive immune response in the intra- hepatic envrionment
NARMADA, B. C.; Khakpoor, A.; SHIRGAONKAR, N.; NARAYANAN, S.; AW, P. P. K.; SINGH, M.; ONG, K. H.; OWINO, C. O.; NG, J. W. T.; YEW, H. C.; BINTE MOHAMED NASIR, N. S.; AU, V. B.; SNG, R.; KALIAPERUMAL, N.; Khine, H. H. T. W.; NG, H. X.; CHIA, S. L.; SEAH, C. X. Y.; HJ ALNAWAZ, M.; WAI, C. L. Y.; TAY, A. Y. L.; YU, W.; CONNOLLY, J. E.; PERIYASAMY, G.; LIM, S. G.; DASGUPTA, R.
Show abstract
Hepatitis B surface antigen (HBsAg) loss or functional cure (FC), is considered the desirable therapeutic outcome for chronic hepatitis B (CHB) patients. However, the immuno-pathological biomarkers and underlying mechanisms remain unclear. Here we present a comprehensive single cell-transcriptomic atlas together with immune-phenotyping of disease-associated cell states (DACS) isolated from intra-hepatic tissue and matched PBMCs of either CHB or FC patients. We find that the intra-hepatic environment displays specific cell identities and molecular signatures that are distinct from PBMCs. FC is associated with emergence of an altered adaptive immune response marked by CD4 cytotoxic T lymphocytes (CD4-CTLs), and an activated innate response represented by liver-resident natural killer (LR-NK) cells. Overall, these findings provide novel insights into immuno-pathological cell states associated with FC that could serve as prognostic biomarkers.
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