Department of Hepatology, Graduate School of Medicine, Osaka City University
Aim: To identify soluble immune checkpoint proteins (sICP) as potential biomarkers for predicting treatment responsiveness in patients with chronic hepatitis B. Methods: The concentrations of 16 sICP were measured using multiplexed fluorescent bead-based immunoassays in sera collected at baseline, 12 weeks, and 48 weeks of treatment. Results: Treatment response was obtained in 6 of the 20 patients (30%) in the nucleos(t)ide analogue (NUC) group of an infinite course ≥48 weeks and in 5 of the 12 patients (42%) in the PegIFNα group of a 48-week finite course. NUC treatment resulted in significant decreases in 10 of the 16 sICPs, most of which were important inhibitory factors including sPD-1, sCTLA-4, sTIM-3 and sCD40. In contrast, during PegIFNα treatment, two inhibitors, sTIM-3 and sLAG-3, increased, while the stimulatory factors sGITRL and sCD40 decreased. The fold changes of sBTLA and sPD-1 in responders by week 12 of PegIFNα treatment were significantly lower than those of the non-responders (P=0.028 and 0.042, respectively). Membrane-bound BTLA and PD-1 were more highly expressed in the PegIFNα and NUC non-responders than in the responders. Conclusion We found different changes in sICPs between NUC-treated and PegIFNα-treated patients. Circulating soluble PD-1 and BTLA proteins are potential biomarkers for prediction of PegIFNα responsiveness.