调节性T细胞（Treg）在维持免疫耐受性和预防自身免疫性疾病中发挥关键作用。最近的数据还表明，类型1调节性T细胞（Tr1）和调节性B细胞（Breg）在自身免疫性疾病中发挥抑制（即保护性）作用。传统合成疾病修饰抗风湿药物（csDMARD）是类风湿性关节炎（RA）的一线治疗，我们的目标是使用免疫表型预测该治疗的临床反应。首先，我们检测了16名健康对照组（HC）和26名RA患者（14名药物未接触患者和12名csDMARD经验患者）新鲜血液中的免疫细胞的存在。然后，我们记录了14名药物未接触患者RA（药物未接触组）在csDMARD治疗之前（即0天）和接受治疗6个月后的免疫表型变化。观察到的变化也与其他临床指标进行了比较，包括抗环瓜氨酸肽抗体（anti-CCP）的存在，类风湿因子（RF）水平，红细胞沉降率（ESR）和C-反应蛋白（CRP）水平。药物未接触组RA患者的Treg明显低于HC和csDMARD经验组患者（p<0.0001），而Treg数量与RA诊断和csDMARD治疗的治疗效果相关。此外，较低基线水平的Treg、记忆性Treg和Tr1以及较高的PD-1+边缘B和Breg细胞与减少的28关节疾病活动评分（DAS28）的发展显著相关（p<0.05），表明具有更好的医疗反应。多元回归和主成分分析确定了Treg、Tr1和Breg作为csDMARD反应的潜在预测因子（曲线下面积：0.9；准确度：92.86%）。此外，较高的Treg、Tr1和Breg细胞与减少的DAS28、ESR和CRP相关（p<0.05）；Treg和Breg细胞表达的变化在具有更好预后的RA患者中的双阴性抗CCP和RF中也更为显著（p<0.05）。免疫表型分析可以作为辅助临床工具，用于识别不适合接受csDMARD治疗的患者。对于这些患者，在疾病早期应制定其他替代治疗干预措施。版权所有©2023，国际抗癌研究学院（George J. Delinasios博士），保留所有权利。

Regulatory T cells (Treg) play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. Recent data also indicate that type 1 regulatory T (Tr1) and regulatory B (Breg) cells play an inhibitory (i.e., protective) role in autoimmune diseases. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) are a first-line therapy for rheumatoid arthritis (RA), and our aim was to predict clinical responses of this treatment using immunophenotyping.We first detected the presence of immune cells in fresh blood from 16 healthy controls (HC) and 26 patients with RA (14 drug-naive and 12 csDMARD-experienced). Then, we recorded immunophenotypic changes in 14 drug-naive RA (naive RA) patients prior to csDMARD treatment (i.e., day 0) and after receiving treatment for 6 months. The observed changes were also compared with other clinical indicators, including the presence of anti-citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels.Naive RA patients had significantly lower Tregs than HC and csDMARD-experienced patients (both p<0.0001) and the number of Tregs correlated with the diagnosis of RA and therapeutic efficacy of csDMARD treatment. Furthermore, lower baseline levels of Treg, memory Treg, Tr1, and higher PD-1+ Marginal B, Breg cells were significantly associated with decreased development of the 28-joint Disease Activity Score (DAS28) (all p<0.05), revealing better medical response. Multiple regression and principal component analysis identified Treg, Tr1, and Breg as potential predictors of csDMARD responses (Area under curve: 0.9; Accuracy: 92.86%). Furthermore, elevated Treg, Tr1, and Breg cells were associated with decreased DAS28, ESR, and CRP (all p<0.05); changes in Treg and Breg cell expression were also more pronounced among double negative anti-CCP and RF in RA patients with better outcomes (p<0.05).Immunophenotyping can be an adjunct clinical tool to identify patients who are poor candidates for csDMARD therapy. Alternative therapeutic interventions in the early stages of disease should be formulated for these patients.Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.