系统性红斑狼疮患者外周血滤泡辅助性T细胞和滤泡调节性T细胞表达变化及意义

Changes in Expression and Significance of Follicular Helper T Cells and Follicular Regulatory T Cells in Peripheral Blood of Patients with Systemic Lupus Erythematosus

摘要: 目的：检测系统性红斑狼疮(SLE)患者外周血中滤泡辅助性T细胞(Tfh)细胞亚型和效应记忆Tfh细胞(Tfh-EM)以及滤泡调节性T细胞(Tfr)的表达，并探讨其在SLE患者发病中的临床意义。方法：流式细胞术分别检测30例SLE患者和26例健康对照的外周血中Tfh (CD4 CXCR5 )细胞亚型Tfh1 (CD4 CXCR5 CXCR3 CCR6⁻)、Tfh2 (CD4 CXCR5 CXCR3⁻CCR6⁻)、Tfh17 (CD4 CXCR5 CXCR3⁻CCR6 )、Tfh-EM (CD4 CXCR5 ICOS PD-1 )和Tfr (CD4 CD25 CXCR5 CD127^low)的水平。收集入组SLE患者的临床资料及实验室指标，采用酶联免疫吸附试验(ELISA)法检测各组受试者外周血中白细胞介素21 (IL-21)。结果：SLE组与健康对照组相比，外周血中Tfh-EM细胞、Tfh17细胞、总Tfh细胞的表达和外周血中IL-21水平较健康对照组表达升高(P均 < 0.05)。SLE组Tfh/Tfr高于健康对照组(P = 0.020)。外周血Tfh-EM细胞在SLE组中高病情活动度的表达高于低疾病活动度的患者(P = 0.024)。Tfh-EM细胞与抗ds-DNA抗体存在正相关(ρ = 0.444, P = 0.018)，Tfr细胞的比率与疾病活动度SLEDAI-2K评分呈负相关(ρ = −0.392, P = 0.039)。结论：SLE组Tfh表达升高致Tfh/Tfr比值失衡，Tfh-EM细胞、Tfh17表达异常可能参与了SLE的发生和发展。

Abstract: Objective: To investigate the expression of follicular helper T cell (Tfh) subtypes and effector memory Tfh cells (Tfh-EM) in the peripheral blood of patients with systemic lupus erythematosus (SLE), as well as the expression of follicular regulatory T cells (Tfr), and to explore their clinical significance in the onset of SLE. Methods: Flow cytometry was utilized to analyze the levels of Tfh (CD4 CXCR5 ) cell subtypes, including Tfh1 (CD4 CXCR5 CXCR3 CCR6⁻), Tfh2 (CD4 CXCR5 CXCR3⁻ CCR6⁻), Tfh17 (CD4 CXCR5 CXCR3⁻CCR6 ), Tfh-EM (CD4 CXCR5 ICOS PD-1 ), and Tfr (CD4 CD25 CXCR5 CD127^low) in the peripheral blood of 30 SLE patients and 26 healthy controls. Clinical data and laboratory parameters of the SLE patients were collected, and enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of interleukin-21 (IL-21) in the peripheral blood of each participant. Results: The expression of Tfh-EM cells, Tfh17 cells, total Tfh cells in peripheral blood and the level of IL-21 in peripheral blood were elevated in the SLE group compared to healthy controls (P all < 0.05). Tfh/Tfr was higher in the SLE group than in healthy controls (P = 0.020), Peripheral blood Tfh-EM cells were expressed higher in the SLE group with high disease activity than in patients with low disease activity (P = 0.024). There was a positive correlation between Tfh-EM cells and anti-ds-DNA antibodies (ρ = 0.444, P = 0.018), and the ratio of Tfr cells was negatively correlated with the SLEDAI-2K score of disease activity (ρ = −0.392, P = 0.039). Conclusion: Elevated Tfh expression in the SLE group resulted in an imbalance of the Tfh/Tfr ratio, and abnormal expression of Tfh-EM cells, Tfh17, may be involved in the occurrence and development of SLE.