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.

doi:10.1101/2022.04.26.489625

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bioRxiv · 10.1101/2022.04.26.489625

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

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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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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.. 2022-04-29. 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. https://doi.org/10.1101/2022.04.26.489625

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