Soluble programmed death-1 levels are associated with disease activity and treatment response in patients with autoimmune hepatitis

Abstract

Purpose: Autoimmune hepatitis (AIH) is a chronic liver disease caused by impaired immune regulation. Programmed death-1 (PD-1) is an inhibitory receptor mainly expressed by T cells and with its ligands, PD-L1 and PD-L2 present on antigen-presenting cells. We hypothesised the PD-1 axis to be impaired in AIH and investigated systemic levels of soluble(s) PD-1 and T cells ability to up-regulate PD-1 following in vitro activation in AIH patients.Materials and methods: We included 67 AIH patients; 9 with active disease, 31 responders and 27 incomplete-responders to standard therapy. Forty-seven healthy controls (HC) were included for comparison. Soluble PD-1 was measured by enzyme-linked immunosorbent assay. The PD-1 expression on T cells was measured using flow cytometry before and after 48-h stimulation in vitro with CD3/CD28 in 13 AIH patients and 10 HC.Results: Soluble PD-1 was significantly elevated in AIH patients with active disease [0.24 ng/mL (range 0.16–0.28)] and in incomplete responders to standard therapy [0.17 (0.11–0.22)] compared with responders [0.11 (0.08–0.16), p = .008 and p = .01, respectively] and HC [0.12 (0.05–0.16), p = .02, both]. Following in vitro activation, PD-1 was significantly up-regulated (3.3-fold) on CD4+ T cells from AIH patients compared with HC (1.5-fold) (p = .0006).Conclusions: AIH patients with active disease and incomplete response to standard treatment have similarly increased sPD-1 levels. Further, AIH patients have increased ability to up-regulate PD-1 following in vitro activation. Together these data suggests an impaired PD-1 axis in AIH.