The significance of the co-stimulatory molecules expression atternation in the peripharal T lymphocytes of patients with chronic hepatitis B infection

Abstract

Objective To investigate the significance of changes in expression of co-stimulatory molecules on T lymphocytes in patients with chronic hepatitis B (CHB) infection. Methods In a case-control study, a total of 82 CHB cases including 50 male cases and 32 female cases (the mean age was 42.32±3.74) were enrolled in the First Affiliated Hospital to Soochow University from October 2012 to November 2013, together with 30 cases health control (15 male cases and 15 female cases, and the mean age was 42.32±3.74). Patients were divided into three groups： 40 cases of non-treated, 30 cases of effective-treated and 12 cases of ineffective-treated with anti-viral drugs and immune-related therapy. The expression levels of CD28, CTLA-4, PD-1, Tim-3 on T cells subset from peripheral blood were determined by Flow Cytometry. Serum load of HBV DNA was detected by Real-time PCR and the serology markers such as HBeAg and ALT were detected by conventional methods The Kruskal-Wallis test was used to analysis groups comparison. Independent samples t-test and Mann-Whitney U test were used to two sample comparison. Spearman′s rank correlation test was used to analyze the correlation. Results The expression levels of CD28, CTLA-4 and PD-1 on CD4 in health control group was the highest compared to ineffective-treated group ［404.65 (331.65-536.09) vs 277.15 (249.90-344.25) (H=29.81, P<0.001); 32.89 (29.69-39.69) vs 19.26 (11.90-20.56) (H=43.13, P<0.001), respectively］. The expression level of PD-1 on CD8 in pre-treated group was the highest ,while expression level in health control group was the lowest ［15.47 (12.50-17.78) vs 3.05 (1.41-3.97) (H=56.60, P<0.001)］. Similarly, the expression level of Tim-3 on CD4 in ineffective-treated group was the highest, while Tim expression on CD4 in health control group was the lowest ［199.62 (55.61-239.45) vs 70.62 (53.88-112.32) (H=41.03, P<0.001)］. The expression level of Tim-3 on CD8 in pre-treated group was the highest, while it was the lowest in health control group ［82.50 (78.69-84.58) vs 3.07(1.56-6.87) (H=74.84, P<0.001)］. Compared to the group with low viral load, the expression level of PD-1 on CD8 both in the pre-treated group with high viral load and the post-treated group was significantly increased ［17.87 (13.38-20.94) (U=25.00, P<0.001); 16.95 (5.39-18.27) (U=63.50, P<0.001), respectively］. Importantly, in the post-treated group, the PD-1 expression on CD4 T (r=0.689, P<0.001) and on CD8 T (r=0.751, P<0.001) was also positively correlated with ALT. Conclusions The abnormal expression of these co-stimulatory molecules may be present in the antiviral treatment process of CHB. It may provide new clues for the reasonable treatment of CHB.（Chin J Lab Med，2014,37：105-109） Key words: Hepatitis B, chronic; T-lymphocytes; Antigens, CD28; CTLA-4 antige; Membrane proteins; Flow cytometry