Laboratory of Immune System Diseases, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
Department of Medicine, University Hospital "Príncipe de Asturias", University of Alcalá and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Alcalá de Henares, 28871 Madrid, Spain.
Cells. 2019 Aug 10;8(8):871. doi: 10.3390/cells8080871.
Patients with long-term, treated, rheumatoid arthritis (RA) show abnormalities in their circulating CD4+ T-lymphocytes, but whether this occurs in recently diagnosed naïve patients to disease-modifying drugs (DMARDs) is under discussion. These patients show heterogeneous clinical response to methotrexate (MTX) treatment. We have examined the count of circulating CD4+ T-lymphocytes, and their naïve (T), central memory (T), effector memory (T) and effector (T) subsets, CD28 expression and Vβ TCR repertoire distribution by polychromatic flow cytometry in a population of 68 DMARD-naïve recently diagnosed RA patients, before and after 3 and 6 months of MTX treatment. At pre-treatment baseline, patients showed an expansion of the counts of CD4+ T, T, T and T lymphocyte subsets, and of total CD4+CD28- cells and of the T subset with a different pattern of numbers in MTX responder and non-responders. The expansion of CD4+T lymphocytes showed a predictive value of MTX non-response MTX treatment was associated to different modifications in the counts of the CD4+ subsets and of the Vβ TCR repertoire family distribution and in the level of CD28 expression in responders and non-responders. In conclusion, the disturbance of CD4+ lymphocytes is already found in DMARD-naïve RA patients with different patterns of alterations in MTX responders and non-responders.
患有长期治疗的类风湿关节炎(RA)的患者其循环 CD4+T 淋巴细胞存在异常,但疾病修饰药物(DMARDs)初诊的未治疗患者是否存在这种情况仍存在争议。这些患者对甲氨蝶呤(MTX)治疗的反应存在异质性。我们通过多色流式细胞术检查了 68 例 DMARD 初治、近期诊断的 RA 患者在 MTX 治疗前、治疗后 3 个月和 6 个月时的循环 CD4+T 淋巴细胞及其幼稚(T)、中央记忆(T)、效应记忆(T)和效应(T)亚群、CD28 表达和 VβTCR 受体库分布。在治疗前基线时,患者的 CD4+T、T、T 和 T 淋巴细胞亚群、总 CD4+CD28-细胞和 MTX 应答者和非应答者中数量不同的 T 亚群计数均有扩增。CD4+T 淋巴细胞的扩增对 MTX 无反应具有预测价值。MTX 治疗与应答者和非应答者中 CD4+亚群计数、VβTCR 受体库家族分布和 CD28 表达水平的不同变化有关。总之,DMARD 初治 RA 患者中已经存在 CD4+淋巴细胞紊乱,且在 MTX 应答者和非应答者中存在不同的改变模式。