Abstract:
Objective To explore the relationship between the histone lysine-specific demethylase 1 (LSD1) expression in CD4+ Th cells and Th1/Th2 cell immune balance of the patients with chronic hepatitis B (CHB), and to explore the effect of histone modifications mediated by LSD1 on the cellular differentiation of CD4+ Th cell in patients with CHB.
Methods A total of 65 patients with CHB hospitalized in the Department of Infectious Disease, Affiliated Hospital of Nantong University, from June to December in 2017 were selected and further divided into different groups according to the serum levels of ALT or HBV-DNA load. 30 healthy persons who received health physical examination during the same period were as the control group. The peripheral blood mononuclear cells were separated with the density gradient centrifugation, and then CD4+ Th cells were sorted using immunomagnetic beads. The total protein of CD4+ Th cells was extracted, the expression of LSD1 was detected using Western blotting. The serum levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were detected using ELISA. The serum HBV-DNA load was detected using real-time qPCR.
Results The expression level of LSD1 in CD4+Th cells in the CHB group was higher than that in the control group (0.52±0.21 vs 0.28±0.09, t=-7.49, P < 0.001). In patients with CHB, the expression level of LSD1 in the high ALT level (>4×ULN) group was lower than that in the low ALT level (≤ 4×ULN) group (0.39±0.18 vs 0.64±0.16, t=-5.79, P < 0.001); the expression level of LSD1 in the high HBV-DNA load (≥ 106 copy/mL) group was higher than that in the low load (< 106 copy/mL) group (0.69±0.08 vs 0.35±0.16, t=10.80, P < 0.001). Compared with the control group, the serum level of IFN-γ and the ratio of IFN-γ/IL-4 was reduced and the serum level of IL-4 was ascending in patients of the CHB group (P < 0.05). The expression level of LSD1 in CD4+Th cells in CHB patients was negatively correlated with the serum levels of ALT (r=-0.590), IFN-γ (r=-0.379), and the ratio of IFN-γ/IL-4 (r=-0.285, P < 0.01), was positively correlated with HBV-DNA load (r=0.880, P < 0.001), and was uncorrelated with the serum level of IL-4 (r=0.169, P=0.102).
Conclusions In the patients with CHB, the high expression of LSD1 could be one of the reasons for the imbalance of Th1/Th2 reaction and descending of Th1 reaction, which can attenuate the elimination of HBV or the inhibition of HBV replication.
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