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 environment

Balakrishnan Chakrapani Narmada; Atefeh Khakpoor; Niranjan Shirgaonkar; Sriram Narayanan; Pauline Poh Kim Aw; Malay Singh; Kok Haur Ong; Collins Oduor Owino; Jane Wei Ting Ng; Hui-Chuing Yew; Nu Soibah Binte Mohamed Nasir; Veonice Bijin Au; Reina Sng; Nivashini Kaliaperumal; Htet Htet Toe Wai Khine; Hui Xin Ng; Su Li Chia; Cindy Xin Yi Seah; Myra HJ. Alnawaz; Chris Lee Yoon Wai; Amy Yuh Ling Tay; Weimiao Yu; John Edward Connolly; Giridharan Periyasamy; Seng Gee Lim; Ramanuj DasGupta

doi:10.1101/2022.04.26.489625

GenomicsbioRxivApr 26, 2022

Preprint

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 environment

Balakrishnan Chakrapani Narmada iD, Atefeh Khakpoor iD, Niranjan Shirgaonkar iD, Sriram Narayanan iD, Pauline Poh Kim Aw iD, Malay Singh iD, Kok Haur Ong iD, Collins Oduor Owino iD, Jane Wei Ting Ng, Hui-Chuing Yew, Nu Soibah Binte Mohamed Nasir, Veonice Bijin Au, Reina Sng iD, Nivashini Kaliaperumal, Htet Htet Toe Wai Khine, Hui Xin Ng, Su Li Chia, Cindy Xin Yi Seah, Myra HJ. Alnawaz, Chris Lee Yoon Wai, Amy Yuh Ling Tay, Weimiao Yu iD, John Edward Connolly, Giridharan Periyasamy iD, Seng Gee Lim iD, Ramanuj DasGupta iD

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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