1. Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment
- Author
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Wen Wei Xiang, Veonice Bijin Au, Amy Tay, Atefeh Khakpoor, John E. Connolly, Cheng Yan, Seng Gee Lim, Bernett Lee, Patricia J. Ahl, Juling Wang, Chris C. Lee, Nivashini Kaliaperumal, and Sriram Narayanan
- Subjects
0301 basic medicine ,HBsAg ,Chemokine ,Time Factors ,Science ,medicine.medical_treatment ,T cell ,Diseases ,Article ,Hepatitis ,03 medical and health sciences ,Hepatitis B, Chronic ,0302 clinical medicine ,Immune system ,Chronic hepatitis ,medicine ,Humans ,Viral hepatitis ,Hepatitis B Surface Antigens ,Multidisciplinary ,CD40 ,biology ,business.industry ,Interferon-alpha ,Bayes Theorem ,Dendritic cell ,Hepatitis B ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,Immunology ,biology.protein ,Medicine ,Cytokines ,Infectious diseases ,030211 gastroenterology & hepatology ,Chemokines ,business - Abstract
Our objective was to examine differences in cytokine/chemokine response in chronic hepatitis B(CHB) patients to understand the immune mechanism of HBsAg loss (functional cure) during antiviral therapy. We used an unbiased machine learning strategy to unravel the immune pathways in CHB nucleo(t)side analogue-treated patients who achieved HBsAg loss with peg-interferon-α(peg-IFN-α) add-on or switch treatment in a randomised clinical trial. Cytokines/chemokines from plasma were compared between those with/without HBsAg loss, at baseline, before and after HBsAg loss. Peg-IFN-α treatment resulted in higher levels of IL-27, IL-12p70, IL-18, IL-13, IL-4, IL-22 and GM-CSF prior to HBsAg loss. Probabilistic network analysis of cytokines, chemokines and soluble factors suggested a dynamic dendritic cell driven NK and T cell immune response associated with HBsAg loss. Bayesian network analysis showed a dominant myeloid-driven type 1 inflammatory response with a MIG and I-TAC central module contributing to HBsAg loss in the add-on arm. In the switch arm, HBsAg loss was associated with a T cell activation module exemplified by high levels of CD40L suggesting T cell activation. Our findings show that more than one immune pathway to HBsAg loss was found with peg-IFN-α therapy; by myeloid-driven Type 1 response in one instance, and T cell activation in the other.
- Published
- 2021