Makris Anastasia, Adamidi Sofia, Koutsianas Christos, Tsalapaki Christina, Hadziyannis Emilia, Vassilopoulos Dimitrios
Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece.
Front Immunol. 2018 Jan 10;8:1967. doi: 10.3389/fimmu.2017.01967. eCollection 2017.
Granulocyte monocyte colony-stimulating factor (GM-CSF) is currently considered a crucial inflammatory mediator and a novel therapeutic target in rheumatoid arthritis (RA), despite the fact that its precise cellular sources remain uncertain. We studied the expression of GM-CSF in peripheral lymphocytes from RA patients and its change with antirheumatic therapies.
Intracellular GM-CSF expression was assessed by flow cytometry in stimulated peripheral B (CD19+) and T (CD3+) cells from RA patients ( = 40), disease ( = 31 including osteoarthritis = 15, psoriatic arthritis = 10, and systemic rheumatic diseases = 6) and healthy ( = 16) controls. The phenotype of GM-CSF+ B cells was assessed as well as longitudinal changes in GM-CSF+ lymphocytes during methotrexate (MTX, = 10) or anti-tumor necrosis factor (anti-TNF, = 10) therapy.
Among untreated RA patients with active disease (Disease Activity Score 28-C-reactive protein = 5.6 ± 0.89) an expanded population of peripheral GM-CSF+ B (4.1 ± 2.2%) and T (3.4 ± 1.6%) cells was detected compared with both disease (1.7 ± 0.9%, < 0.0001 and 1.7 ± 1.3%, < 0.0001, respectively) and healthy (0.3 ± 0.2%, < 0.0001 and 0.6 ± 0.6%, < 0.0001) controls. RA GM-CSF+ B cells displayed more commonly a plasmablast or transitional phenotype (37.12 ± 18.34% vs. 14.26 ± 9.46%, = 0.001 and 30.49 ± 15.04% vs. 2.45 ± 1.84%, < 0.0001, respectively) and less a memory phenotype (21.46 ± 20.71% vs. 66.99 ± 16.63%, < 0.0001) compared to GM-CSF- cells. GM-CSF expression in RA patients did not correlate to disease duration, activity or serological status. Anti-TNF treatment led to a statistically significant decrease in GM-CSF+ B and T cells while MTX had no significant effect.
This is the first study showing an expanded population of GM-CSF+ B and T lymphocytes in patients with active RA which declined after anti-TNF therapy.
粒细胞-巨噬细胞集落刺激因子（GM-CSF）目前被认为是类风湿关节炎（RA）中一种关键的炎症介质和新的治疗靶点，尽管其确切的细胞来源仍不确定。我们研究了GM-CSF在RA患者外周淋巴细胞中的表达及其在抗风湿治疗后的变化。
采用流式细胞术评估来自RA患者（n = 40）、疾病对照组（n = 31，包括骨关节炎患者15例、银屑病关节炎患者10例和系统性风湿性疾病患者6例）和健康对照组（n = 16）的外周B（CD19 +）和T（CD3 +）细胞在刺激后细胞内GM-CSF的表达。评估GM-CSF + B细胞的表型以及甲氨蝶呤（MTX，n = 10）或抗肿瘤坏死因子（抗TNF，n = 10）治疗期间GM-CSF +淋巴细胞的纵向变化。
在疾病活动的未治疗RA患者中（疾病活动评分28- C反应蛋白= 5.6±0.89），与疾病对照组（分别为1.7±0.9%，P < 0.0001和1.7±1.3%，P < 0.0001）和健康对照组（0.3±0.2%，P < 0.0001和0.6±0.6%，P < 0.0001）相比，外周GM-CSF + B（4.1±2.2%）和T（3.4±1.6%）细胞群体有所扩大。与GM-CSF -细胞相比，RA GM-CSF + B细胞更常表现为浆母细胞或过渡型表型（分别为37.12±18.34%对14.26±9.46%，P = 0.001和30.49±15.04%对2.45±1.84%，P < 0.0001），而记忆型表型较少（21.46±20.71%对66.99±16.63%，P < 0.0001）。RA患者中GM-CSF的表达与疾病持续时间、活动度或血清学状态无关。抗TNF治疗导致GM-CSF + B和T细胞在统计学上显著减少，而MTX没有显著影响。
这是第一项显示活动期RA患者中GM-CSF + B和T淋巴细胞群体扩大且在抗TNF治疗后减少的研究。
