Xue Meilang, Lin Haiyan, Lynch Tom, Chand Vibhasha, Sinnathurai Premarani, Thomas Ranjeny, Keen Helen, Hill Catherine, Lester Susan, Wechalekar Mihir, Lassere Marissa, March Lyn
Sutton Arthritis Research Laboratory, Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2065, Australia.
The Australian Arthritis and Autoimmune Biobank Collaborative (A3BC), Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2065, Australia.
J Clin Med. 2025 Jun 13;14(12):4220. doi: 10.3390/jcm14124220.
: This study compared the frequencies of circulating CD4+ T helper (Th) cell subsets in rheumatoid arthritis (RA) patients and healthy controls (HCs) and investigated their relationship with RA disease activity. : Peripheral blood samples and demographic/clinical data were collected from 75 RA patients and 28 HCs from the A3BC Biobank. Flow cytometry was utilized to identify cell subsets. Data were analyzed using FlowJo and GraphPad Prism. : RA patients displayed altered Th cell subset frequencies compared with HCs, including a higher overall proportion of Th cells ( = 0.02) but lower proportions of memory Th ( = 0.03), Th1 ( < 0.0001), and Th17.1 ( = 0.004) cells. In DMARD-naïve RA patients ( = 16), lower proportions of Th1 ( = 0.0005), Th9 ( = 0.04), and Th17.1 ( = 0.003) cells, alongside a higher Th17 cell proportion ( = 0.017), were observed compared with those in HCs. Further analysis of matched treatment-naïve, new-onset RA patients and HCs confirmed these findings. Within the RA cohort, lower proportions of Th1 ( = 0.002) and Th17.1 ( = 0.025) cells and a higher proportion of Th2 cells ( = 0.015) were correlated with increased disease activity. Inverse correlations were also found between the proportions of Th1 ( = 0.002), Th9 ( = 0.024), and Th17.1 ( = 0.00017) cells and CRP levels in RA patients. : This study demonstrates an imbalance in circulating Th cell subset frequencies in RA patients compared with those in HCs, with notably lower Th1 and Th17.1 cell proportions in RA patients. Decreased frequencies of these cell subsets were linked to increased disease activity, indicating that restoring the balance of Th cell subsets could be a potential therapeutic strategy for RA.
本研究比较了类风湿关节炎(RA)患者和健康对照者(HCs)循环中CD4+辅助性T(Th)细胞亚群的频率,并研究了它们与RA疾病活动度的关系。从A3BC生物样本库收集了75例RA患者和28例HCs的外周血样本以及人口统计学/临床数据。利用流式细胞术鉴定细胞亚群。数据使用FlowJo和GraphPad Prism进行分析。与HCs相比,RA患者的Th细胞亚群频率发生改变,包括Th细胞总体比例较高(P = 0.02),但记忆性Th细胞比例较低(P = 0.03)、Th1细胞比例较低(P < 0.0001)以及Th17.1细胞比例较低(P = 0.004)。在未使用改善病情抗风湿药(DMARD)的RA患者(n = 16)中,与HCs相比,观察到Th1细胞比例较低(P = 0.0005)、Th9细胞比例较低(P = 0.04)以及Th17.1细胞比例较低(P = 0.003),同时Th17细胞比例较高(P = 0.017)。对配对的未治疗、新发RA患者和HCs的进一步分析证实了这些发现。在RA队列中,Th1细胞比例较低(P = 0.002)和Th17.1细胞比例较低(P = 0.025)以及Th2细胞比例较高(P = 0.015)与疾病活动度增加相关。在RA患者中,还发现Th1细胞比例(P = 0.002)、Th9细胞比例(P = 0.024)和Th17.1细胞比例(P = 0.00017)与C反应蛋白(CRP)水平呈负相关。本研究表明,与HCs相比,RA患者循环中Th细胞亚群频率失衡,RA患者中Th1和Th17.1细胞比例显著较低。这些细胞亚群频率降低与疾病活动度增加相关,表明恢复Th细胞亚群平衡可能是RA的一种潜在治疗策略。