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

Zhonghua Gan Zang Bing Za Zhi. 2019 Jul 20;27(7):541-546. doi: 10.3760/cma.j.issn.1007-3418.2019.07.012.
[Article in Chinese]

Abstract

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(-)CD27(hi)CD38(hi)), 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.

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(-)CD27(hi)CD38(hi))、初始B细胞(CD19(+)CD10(-)CD27(-)IgD(+))、transitional B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。.

Keywords: Hepatitis, autoimmune; Liver damage; Plasma cells; T-box expressed in T cell.

MeSH terms

  • B-Lymphocyte Subsets / metabolism
  • Flow Cytometry
  • Hepatitis, Autoimmune / pathology*
  • Humans
  • Plasma Cells / metabolism*
  • T-Box Domain Proteins / metabolism*

Substances

  • T-Box Domain Proteins
  • T-box transcription factor TBX21