Aberrant production of soluble co-stimulatory molecules CTLA-4 and CD28 in patients with chronic hepatitis B

Co-stimulation signals are critical for anti-viral immunity. Here we investigated whether there is altered expression and the clinical significance of soluble co-stimulatory molecules in patients with chronic HBV infection. Serum concentrations and ex vivo production of soluble CTLA-4, CD28, CD80 and CD86 were analyzed by enzyme-linked immunosorbent assay. Serum sCTLA-4 and sCD28 concentrations in all chronic HBV patients were significantly higher than concentrations in healthy control subjects. Serum sCTLA-4 and sCD28 correlated significantly with alanine aminotransferase in all chronic HBV patients. Upon mitogen stimulation of peripheral blood mononuclear cells, the percentage increases in ex vivo production of sCD28 and sCD80 and the percentage decrease in sCTLA-4 release were all significantly lower in chronic HBV patients than those in healthy subjects. The aberrant production of soluble co-stimulatory molecules should reflect the dysregulation of T cell activation and is related to the pathogenesis and severity of chronic HBV infection.

► There was aberrant production of soluble co-stimulatory molecules CTLA-4 and CD28 in patients with chronic hepatitis B. ► Serum sCTLA-4 and sCD28 correlated significantly with ALT in all chronic HBV patients. ► There was a significant and positive correlation between serum sCTLA-4 and sCD28, or sCD28 and sCD86 in chronic HBV patients.