Th Cell Phenotypes and Their Correlations with Disease Activity in Patients with Rheumatoid Arthritis

<b>Objectives</b>: 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. <b>Methods</b>: 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. <b>Results</b>: RA patients displayed altered Th cell subset frequencies compared with HCs, including a higher overall proportion of Th cells (<i>p</i> = 0.02) but lower proportions of memory Th (<i>p</i> = 0.03), Th1 (<i>p</i> < 0.0001), and Th17.1 (<i>p</i> = 0.004) cells. In DMARD-naïve RA patients (<i>n</i> = 16), lower proportions of Th1 (<i>p</i> = 0.0005), Th9 (<i>p</i> = 0.04), and Th17.1 (<i>p</i> = 0.003) cells, alongside a higher Th17 cell proportion (<i>p</i> = 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 (<i>p</i> = 0.002) and Th17.1 (<i>p</i> = 0.025) cells and a higher proportion of Th2 cells (<i>p</i> = 0.015) were correlated with increased disease activity. Inverse correlations were also found between the proportions of Th1 (<i>p</i> = 0.002), Th9 (<i>p</i> = 0.024), and Th17.1 (<i>p</i> = 0.00017) cells and CRP levels in RA patients. <b>Conclusions</b>: 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.