目的:探讨接受Janus激酶抑制剂(JAKis)治疗的类风湿关节炎(RA)患者B细胞亚群的分布和活化情况,并分析其与疾病缓解的相关性。
方法:收集23名成人健康对照组和58名RA患者的外周血样本,其中31人接受了JAKis治疗,并在24个月的随访中进行了评估。外周B细胞亚群(包括幼稚B细胞,非交换存储器B(NSMB)单元,开关记忆B单元,和双阴性B细胞),他们的激活,通过流式细胞术分析每个群体中B细胞受体(BCR)刺激后SYK和AKT的磷酸化。
结果:与健康对照组相比,在新发病的未经治疗的RA患者中,NSMB细胞的频率显著降低.然而,CD40,CD80,CD95,CD21low和pAKT在这些NSMB细胞中的表达显着增加。此外,在这些患者中,NSMB细胞的数量与DAS28-ESR以及IgG和IgA水平呈负相关;NSMB细胞上CD80,CD95和CD21low的表达与DAS28-ESR以及IgG和IgA水平呈正相关。用JAKis治疗后,缓解期RA患者血清IgG浓度显著降低,但NSMB细胞中CD40、CD95和pAKT水平显著降低。
结论:RA患者呈现不同的B细胞亚群,其中NSMB细胞的频率与疾病活动呈负相关。然而,用JAKis治疗可以抑制NSMB细胞的活化,恢复激酶磷酸化的平衡,并促进RA患者的疾病缓解。
OBJECTIVE: To investigate the distribution and activation of B-cell subpopulations in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) and to analyze their correlation with disease remission.
METHODS: Peripheral blood samples were collected from 23 adult healthy controls and 58 RA patients, 31 of whom were treated with JAKis and assessed during a 24-month follow-up. The number of peripheral B-cell subpopulations (including naive B cells, nonswitched memory B (NSMB) cells, switched memory B cells, and double-negative B cells), their activation, and phosphorylation of SYK and AKT upon B-cell receptor (BCR) stimulation in each population were analyzed by flow cytometry.
RESULTS: Compared with that in healthy controls, the frequency of NSMB cells was significantly lower in new-onset untreated RA patients. However, expression of
CD40, CD80, CD95, CD21low and pAKT significantly increased in these NSMB cells. Additionally, the number of NSMB cells correlated negatively with DAS28-ESR and IgG and IgA levels in these patients; expression of CD80, CD95 and CD21low on NSMB cells correlated positively with DAS28-ESR and IgG and IgA levels. After treatment with JAKis, the serum IgG concentration significantly decreased in RA patients in remission, but
CD40, CD95 and pAKT levels in NSMB cells significantly decreased.
CONCLUSIONS: RA patients present different B-cell subpopulations, in which the frequency of NSMB cells is negatively associated with disease activity. However, treatment with JAKis can inhibit activation of NSMB cells, restore the balance of kinase phosphorylation, and facilitate disease remission in RA patients.