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. 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. 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. 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.

中文翻译：

---

JAK 抑制剂可减轻类风湿关节炎缓解期患者非转换记忆 B 细胞的过度激活


目的 研究接受 Janus 激酶抑制剂 (JAKis) 治疗的类风湿性关节炎 (RA) 患者中 B 细胞亚群的分布和激活，并分析其与疾病缓解的相关性。从 23 名成年健康对照者和 58 名 RA 患者中采集外周血样本，其中 31 名患者接受了 JAK 治疗，并在 24 个月的随访期间进行了评估。外周 B 细胞亚群（包括初始 B 细胞、非转换记忆 B (NSMB) 细胞、转换记忆 B 细胞和双阴性 B 细胞）的数量、它们的激活以及 B 细胞受体上 SYK 和 AKT 的磷酸化（通过流式细胞术分析每个群体的 BCR) 刺激。与健康对照相比，新发未治疗的 RA 患者中 NSMB 细胞的频率明显较低。然而，这些 NSMB 细胞中 CD40、CD80、CD95、CD21low 和 pAKT 的表达显着增加。此外，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。 JAKis治疗后，缓解期RA患者血清IgG浓度显着降低，但NSMB细胞中CD40、CD95和pAKT水平显着降低。 RA 患者存在不同的 B 细胞亚群，其中 NSMB 细胞的频率与疾病活动度呈负相关。然而，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。