慢性乙型肝炎患者外周血T淋巴细胞表面共刺激分子的表达变化及临床意义

Clinical significance of the co-stimulatory molecule expression in the peripheral T lymphocytes of patients with chronic hepatitis B infection

目的探讨T淋巴细胞表面共刺激分子在慢性乙型肝炎（CHB）患者外周血中的表达及其临床意义。方法选取我院在2013年3月至2014年3月期间收治的126例CHB患者和90例健康对照者作为研究对象，利用流式细胞术和定量PCR检测CHB患者和健康对照者外周血中T淋巴细胞表面共刺激分子CD28、细胞毒性T淋巴细胞抗原（CTLA）-4、程序性死亡分子（PD）-1、T细胞免疫球蛋白粘蛋白分子（Tim）-3及T淋巴细胞亚群的表达变化，并进行比较分析。结果CHB患者外周血CD3^＋、CD4^＋T细胞百分率及CD4^＋／CD8^＋比值均低于对照组，而CD8^＋T细胞百分率高于对照组，组间比较差异具有统计学意义（分别t=4．0868，7．4660，5．5207和3．8160，均P〈0．01）；同时，HBVDNV阳性组患者外周血CD3^＋、CD4^＋T细胞百分率及CD4^＋／CD8^＋比值均低于HBVDNA阴性组，而CD8^＋T细胞百分率高于HBVDNA阴性组，组问比较差异具有统计学意义（分别t=5．1567，2．7884，2．9987和2．9087，均P〈0．01）；此外，CHB患者外周血共刺激分子CD28^＋及CTLA-4^＋的表达量均低于正常对照组，而PD-1和Tim-3的表达量高于对照组，差异具有统计学意义（分别t=6．0546，5．0669和6．3006，8．2151，均P〈0．01）；同时，HBVDNA阳性高拷贝组患者外周血共刺激分子CD28及cTLA-4的表达量均低于低拷贝组，而PD-1和Tim-3的表达量高于低拷贝组，组间比较差异具有统计学意义（分别t=3．1293，2．7459，2．8661，2．7960，均P〈0．01）。结论外周血T淋巴细胞亚群及其表面共刺激分子的表达水平对于指导CHB患者的临床治疗和判断预后具有一定的临床意义。

Objective To investigate the changes in the expression of co-stimulatory molecules in the peripheral blood T lymphocyte subsets in patients with chronic hepatitis B infection. Methods 126 patients with chronic hepatitis B who got medical treatment in our hospital from 2013 March to 2014 March, together with 90 healthy subjects were enrolled in our case-control study,We determined the expression levels of CD28, cytotoxic T lymphocyte antigen（CTLA）-4, programmed cell death （PD）-1, T cell immunoglobulin domain and mucin domaim（Tim）-3, CD3^＋, CD4^＋ , CD8^＋, CD4^＋/CD8^＋ on peripheral blood T lymphocyte subsets with flow cy- tometry and Real-time PCR. Results The percentage of CD3^＋ and CD4^＋ T cells, CD4^＋/CD8^＋ ratio in patients with chronic hepatitis B were significantly lower than those in healthy control, and the percentage of CD8^＋ T cells was significantly higher than in healthy conntrol （t = 4. 0868,7. 4660,5. 5207 and 3. 8160, all P 〈 0. 01 ）. Meanwhile,compared with the HBV DNA-negative patients with chronic hepatitis B infection（ CHB）, the HBV DNA-positive patients with CHB had a significant change in the percentage of CD3^＋, CD^＋ and CD8^＋ T cells , as well as in the CD4^＋/CD8^＋ ratio （ t = 5. 1567,2. 7884,2.9987and 2. 9087, all P 〈 0.01 ）. Besides, the percentage of CD28 and CTLA-4 in patients with chronic hepatitis B were significantly lower than those in healthy control, and the percentage of PD-I and Tim-3 were significantly higher than those in healthy conntrol（ t = 6.0546,5. 0669 and 6.3006,8.2151, all P 〈 0.01 ）. The percentage of CD28 and CTLA-4 in patients with high copies group were significantly lower than those in low copies group,and the percentage of PD-1 and Tim-3 were significantly higher than those in low copy group （t = 3. 1293,2.7459,2.8661,2. 7960, all P 〈 0. 01 ）. Conclusion The changes in the expression of co-stimulatory molecules on the peripheral blood T lymphocyte subsets may guide the clinical therapy and judge the prognosis in patients with chronic hepatitis B infection.