Data Sheet 1_Increased sputum peripheral helper T cells are associated with the severity of rheumatoid arthritis but not with the severity of airway disease.pdf

ObjectivePeripheral helper T (Tph) cells, together with plasma cells, are the major pathogenic lymphocytes in the synovium in rheumatoid arthritis (RA). However, whether these cells are involved in RA-associated lung and/or airway disease is unknown.
MethodsTph cells in sputum were analyzed by flow cytometry and compared with those in synovial fluid and synovial tissue. Forty RA subjects for whom induced sputum could be collected were analyzed along with sputum Tph cells and several clinical parameters; RA severity was assessed using the Disease Activity Score for 28 joints (DAS28). Lung and airway disease was assessed by chest computed tomography (CT), pulmonary function test, the chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), and sputum culture. Tph cells in the lung of RA subjects were analyzed using lung resection samples in a separate cohort.
ResultsTph cells were observed in the sputum, as well as the lung, synovial fluid, and synovial tissue of RA patients. Sputum Tph cells were increased in patients with airway disease. Among these patients, Tph cells were more frequent in those with high DAS28, high serum immunoglobulin G (IgG), and high sputum IgG. However, there was no association between Tph cells and the severity of airway disease as assessed by chest CT findings, lung function, CAT, and sputum culture.
ConclusionsTph cells were increased in the airways as well as in the synovium in patients with RA. Airway Tph cells were associated with severity of RA but not with the severity of airway disease. Airway Tph cells may represent a novel target for disease management and treatment.

研究目的：外周辅助性T细胞（Peripheral helper T, Tph）与浆细胞是类风湿关节炎（rheumatoid arthritis, RA）患者滑膜组织中主要的致病性淋巴细胞。目前尚不清楚此类细胞是否参与RA相关肺部及气道疾病的发生发展。
研究方法：采用流式细胞术对痰液中的Tph细胞进行分析，并与滑膜液及滑膜组织中的Tph细胞进行对比。本研究纳入40例可采集诱导痰的RA患者，对其痰液中的Tph细胞及多项临床参数进行分析；采用28个关节疾病活动度评分（Disease Activity Score for 28 joints, DAS28）评估RA疾病严重程度。通过胸部计算机断层扫描（computed tomography, CT）、肺功能检查、慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）评估测试（CAT）以及痰培养对患者的肺部及气道疾病进行评估。另外，在另一独立队列中，利用肺切除样本对RA患者肺部的Tph细胞进行分析。
研究结果：在RA患者的痰液、肺部、滑膜液及滑膜组织中均检测到Tph细胞。合并气道疾病的患者痰液中的Tph细胞水平升高。在该类患者中，DAS28评分高、血清免疫球蛋白G（immunoglobulin G, IgG）水平高以及痰液IgG水平高的患者，其Tph细胞占比更高。不过，通过胸部CT影像、肺功能、CAT评分及痰培养评估的气道疾病严重程度与Tph细胞水平并无关联。
研究结论：RA患者的气道与滑膜组织中Tph细胞水平均升高。气道Tph细胞与RA疾病严重程度相关，但与气道疾病严重程度无关。气道Tph细胞或可成为RA疾病管理与治疗的全新靶点。