使用 Treg、Tr1 和 Breg 表达水平预测初治类风湿关节炎患者对 csDMARD 治疗的临床反应。

Using Treg, Tr1, and Breg Expression Levels to Predict Clinical Responses to csDMARD Treatment in Drug-naive Patients With Rheumatoid Arthritis.

机构信息

School of Medicine, National Defense Medical Center, Taipei, Taiwan, R.O.C.

Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

In Vivo. 2023 Sep-Oct;37(5):2018-2027. doi: 10.21873/invivo.13299.

DOI:10.21873/invivo.13299

PMID:37652509

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10500538/

Abstract

BACKGROUND/AIM: 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.

MATERIALS AND METHODS

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.

RESULTS

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).

CONCLUSION

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.

摘要

背景/目的：调节性 T 细胞（Treg）在维持免疫耐受和预防自身免疫性疾病方面发挥着关键作用。最近的数据还表明，1 型调节性 T（Tr1）和调节性 B（Breg）细胞在自身免疫性疾病中发挥抑制（即保护）作用。传统的合成疾病修饰抗风湿药物（csDMARD）是类风湿关节炎（RA）的一线治疗药物，我们的目的是使用免疫表型来预测这种治疗的临床反应。

材料和方法

我们首先检测了 16 名健康对照者（HC）和 26 名 RA 患者（14 名初治和 12 名 csDMARD 经验）新鲜血液中免疫细胞的存在。然后，我们记录了 14 名初治 RA（naive RA）患者在接受 csDMARD 治疗前（即第 0 天）和治疗 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，包括抗瓜氨酸肽抗体（抗 CCP）、类风湿因子（RF）水平、红细胞沉降率（ESR）和 C 反应蛋白（CRP）水平。

结果

naive RA 患者的 Treg 明显低于 HC 和 csDMARD 经验患者（均 p<0.0001），且 Treg 的数量与 RA 的诊断和 csDMARD 治疗的疗效相关。此外，较低的 Treg、记忆性 Treg、Tr1 和较高的 PD-1+Marginal B、Breg 细胞的基线水平与 28 关节疾病活动评分（DAS28）的降低显著相关（均 p<0.05），表明对治疗有更好的反应。多元回归和主成分分析确定 Treg、Tr1 和 Breg 为 csDMARD 反应的潜在预测因子（曲线下面积：0.9；准确性：92.86%）。此外，Treg、Tr1 和 Breg 细胞的升高与 DAS28、ESR 和 CRP 的降低相关（均 p<0.05）；在 RA 患者中，Treg 和 Breg 细胞表达的变化在抗 CCP 和 RF 双阴性且预后较好的患者中更为明显（p<0.05）。