Background: Rheumatoid arthritis (RA) is an immune-mediated disease and primarily affects the synovium. The goal of treatment in RA is remission (1), however we do not routinely assess immunological markers or perform ultrasound imaging to define this.

背景:  类风湿关节炎（RA）是一种免疫介导的疾病，主要影响滑膜。RA的治疗目标是缓解，但我们并没有惯常评估免疫标志物或用超声成像确定这一点。

Objectives: We aimed to explore the clinical, imaging and immunological characteristics of RA patients in clinical remission (DAS28<2.6).

目的: 本研究的目的旨在探讨RA临床缓解（DAS28 < 2.6）患者临床、影像学和免疫学特征。

Methods: A retrospective observational study was performed, using our inflammatory arthritis database. Patients were selected when fulfilling the inclusion criteria of RA diagnosis (1987 or 2010 ACR/EULAR criteria) and DAS28CRP≤3.2. The lowest observation of DAS28CRP after diagnosis and the availability of ultrasound data were prioritised. Disease/remission duration and treatment modality were not considered in this initial descriptive study. We collected data of: Tender and swollen joint counts, inflammatory markers, autoantibodies, patient-reported outcomes (PRO’s), ultrasound and x-ray findings. Furthermore, T-cell subsets [naïve CD4+T-cells, Inflammation related cells (IRC), and regulatory T-cells (Treg)] were measured and analysed by advanced 8 colour flow-cytometry. Frequencies of T-cells   were compared with reference range values obtained from 120 healthy controls.

方法: 我们用炎性关节炎的数据库进行一项回顾性观察研究。RA患者入选需满足1987年或2010年ACR/ EULAR诊断标准和DAS28CRP≤3.2。诊断后DAS28CRP最低值和超声资料的可用性按优先次序区分。疾病/缓解持续时间和治疗方式在最初的描述性研究并没有收集。我们收集的资料有：疼痛和肿胀关节数、炎症标志物、自身抗体、患者报告结果（PRO’s）、超声和X线结果。同时，由先进8色流式细胞术分析T细胞亚群 [幼稚CD4 ⁺ T细胞，炎症相关细胞（IRC）和调节性T细胞（Treg）]。 T细胞的百分率与来自120名健康对照获得的参考值范围进行比较。

Results: We included 633 patients with a minimum DAS28CRP≤3.2 (mean 1.85/SD 0.67).  The cohort was predominantly female (68.7%) and the mean age was 57.6 years. Of these, 513 were in DAS-defined remission. LDA was included as a control. In the remission group, 324 patients had ultrasound data available. Active synovitis, confirmed by positive Power Doppler signal was present in 43.2% (140/324) of patients. 76.2% (247/324)  had evidence of grey scale (GS) changes >1 in ≥1 joint. For 51 patients where T-cell subset analysis was available, abnormal frequencies were observed in 11.8% of patients for naïve CD4+T-cells, 27.5% for IRC and 54.9% for Treg in the total cohort. For patients in remission, abnormal cell frequencies were seen in 8.7% (4/46), 23.9% (11/46) and 50% (23/46)  for naïve, IRC and Treg's respectively. In LDA 65.3% (47/72) had evidence of Power Doppler synovitis and 86.1% (62/72) had GS changes >1 in ≥1 joint. Abnormal cell frequencies were found in 40% (2/5) of patients for naïve CD4 + T-cells, 60% (3/5) for IRC and all had abnormal Treg frequencies. The remission group had generally low levels of disability, functional and life impairment as expected.

结果: 本研究包括633例RA患者，DAS28CRP≤3.2（平均1.85/0.67 SD）。队列为以女性为主（68.7％），平均年龄为57.6岁。这些患者中，513例为疾病缓解。LDA（低疾病活动度）患者作为对照。在缓解组，324例患者有超声数据。正能量多普勒证实有活动性滑膜炎的患者有43.2％（140/324）。 在≥1关节中76.2％（247/324）证实有灰度（GS）变化>1。51例患者有T细胞亚群的资料。观察到11.8％的患者有异常的幼稚CD4+ T细胞百分率，27.5％的患者IRC百分率异常和54.9％Treg细胞百分率异常。临床缓解的患者中，异常T细胞百分率患者占比分别为幼稚8.7％（4/46），IRC 23.9％（11/46）和Treg 50％（23/46）。在LDA患者中，正能量多普勒证实有滑膜炎的患者有65.3％（47/72）和86.1％（62/72）的患者≥1关节GS变化>1。异常T细胞百分率患者占比分别为幼稚CD4 ⁺ T细胞40％ （2/5），IRC 60％（3/5）和Treg 100%（5/5）。与预期的结果一致，缓解组较低水平的致残、功能和生活障碍。

Conclusions: Despite being in clinical/DAS remission or LDA state, a substantial proportion of patients exhibit subclinical inflammation on ultrasound (higher for LDA). T-cell abnormalities were present in the majority. Current remission criteria are composite scores and do not measure inflammation directly (1). Identification of remission biomarkers could potentially help predict the ability to sustain remission and facilitate treatment withdrawal strategies, leading to a better understanding of what constitutes true remission.

结论: 尽管处于临床/ DAS缓解或LDA状态，患者有相当比例表现出超声下亚临床炎症反应（LDA者更高）。 T细胞的异常也存在于大多数患者中。当前缓解标准是综合得分并没有直接测量炎症。缓解的生物标志物的鉴定可能有助于预测维持缓解和治疗停药的策略，从而更好地理解什么是真正的缓解。

References:

1. Saleem et al. Can remission be maintained with or without further drug therapy in rheumatoid arthritis? Clinical and experimental rheumatology. 2006 Nov-Dec; 24((6 Suppl 43)):S-33-36.