自身免疫性肝炎患者外周血浆细胞T-bet表达水平升高与肝损害的相关性

Study of the correlation between elevated level of T-bet expression and liver damage in peripheral plasma cells of patients with autoimmune hepatitis

目的研究自身免疫性肝炎(AIH)患者外周血浆细胞T-bet表达水平与肝损害的相关性,为疾病发生和发展的机制研究提供参考。方法收集29例AIH患者和6例健康志愿者的静脉血及临床检验资料,流式细胞技术检测外周血B细胞各亚群的比例和各亚群T-bet^+细胞的比例,其中B细胞亚群包括浆细胞(CD19^+CD10-CD27hiCD38hi)、初始B细胞(CD19^+CD10-CD27-IgD^+)、transitionalB细胞(CD19^+CD10^+)和记忆B细胞(CD19^+CD10-CD27^+IgD-)。将血清免疫球蛋白G(IgG)与丙氨酸氨基转移酶(ALT)水平,外周血各亚群B细胞比例与IgG水平,T-bet^+细胞在各亚群中的比例与各亚群在B细胞中的比例,T-bet^+浆细胞比例和血清ALT水平做相关分析,采用两独立样本t检验和线性回归进行统计学分析。结果ALT异常组的AIH患者血清IgG水平(19.47±1.039)g/L显著高于ALT正常组患者的IgG水平(15.5±1.069)g/L,差异有统计学意义(t=2.65,P<0.05)。AIH患者外周血浆细胞占B细胞的比例2.80%±0.14%高于健康对照的外周血浆细胞占B细胞比例0.73%±0.09%,差异有统计学意义(P<0.01);AIH患者外周血浆细胞中T-bet^+细胞比例23.54%±1.61%高于健康对照外周血浆细胞中T-bet^+细胞比例6.59%±0.59%,差异有统计学意义(P<0.01)。相关分析显示,AIH患者外周血浆细胞中T-bet^+细胞比例与浆细胞比例占B细胞比例呈正相关(r=0.2247,P<0.01),外周血浆细胞占B细胞比例与血清IgG水平呈正相关(r=0.2991,P<0.01),血清IgG水平与反映肝损害的指标ALT水平相关(t=2.65,P<0.05)。结论AIH患者外周血浆细胞中T-bet的表达水平升高与肝损害相关,是AIH发病及病情发展的新机制。

Objective To study the correlation between the level of T-bet expression and liver damage in peripheral plasma cells of patients with autoimmune hepatitis (AIH) in order to provide reference for the study of pathogenesis and development of diseases. Methods The peripheral venous blood and clinical examination data of 29 cases with AIH and 6 healthy volunteers were collected. The percentage of subpopulations of peripheral blood B cells and the proportion of T-bet^+ cells in each subgroup were detected by flow cytometry. Plasma cells (CD19^+CD10-CD27hiCD38hi), primary B cells (CD19^+CD10-CD27-IgD^+), transitional B cells (CD19^+CD10^+), and memory B cells (CD19^+CD10-CD27^+IgD-) were the included subsets of B cells. Serum immunoglobulin G (IgG) and alanine aminotransferase (ALT) levels, the proportion of B cells in peripheral blood subsets and IgG level, the proportion of T-bet^+ cells in each subset and the proportion of T-bet^+ plasma cells in each subset in B cells, the proportion of T-bet^+ plasma cells and the level of serum ALT were analyzed for correlation analysis. Statistical analysis was performed using two independent sample t-tests and linear regression. Results The serum IgG level of AIH patients with abnormal ALT (19.47 ± 1.039)g/L was significantly higher than that of normal ALT patients (15.5 ± 1.069)g/L, and the difference was statistically significant (t = 2.65, P < 0.05). The percentage of peripheral plasma cells in B cells of AIH patients (2.80 ± 0.14)% was higher than that of healthy volunteers (0.73 ± 0.09)%, and the difference was statistically significant (P < 0.01). The percentage of T-bet^+ cells in peripheral plasma cells of AIH patients (23.54 ± 1.61)% was higher than that of healthy volunteers (6.59±0.59)%, and the difference was statistically significant (P < 0.01). The correlation analysis showed that the proportion of T-bet^+ cells in peripheral plasma cells of AIH patients was positively correlated with the proportion of plasma cells to B cells (r = 0.224 7, P < 0.01), and the percentage of peripheral plasma cells to B cells was positively correlated with the level of serum IgG (r = 0.299 1, P < 0.01). Serum IgG level was correlated with the level of ALT, reflecting an indicator of liver damage (t = 2.65, P < 0.05). Conclusion The increase of T-bet expression in the peripheral plasma cells of AIH patients is associated with liver damage, which is a new mechanism of AIH pathogenesis and disease progression.