Tung Chien-Hsueh, Lu Ming-Chi, Lai Ning-Sheng, Wu Shu-Fen
Division of Allergy, Immunology and Rheumatology; Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chiayi, Taiwan, Republic of China.
School of Medicine, Tzu Chi University, Hualien, Taiwan, Republic of China.
PLoS One. 2017 Aug 24;12(8):e0183726. doi: 10.1371/journal.pone.0183726. eCollection 2017.
CD154 (commonly referred to as CD40-ligand) is a critical T cell factor that participates in the pathogenesis of autoimmune and is over-expressed in rheumatoid arthritis (RA). TNF-α blockade treatment had dramatic efficacy in RA.
To investigate whether TNF-α blockade treatment can inhibit CD154 expression in RA.
Blood samples were collected from 33 patients with rheumatoid arthritis before and 3 months after TNF-α blockade treatment. Clinical serological data determined by standard assays and T cell CD154 expression levels determined by flow cytometry were statistically analyzed for these two time points.
The percentage of CD154 expression on gated CD4+ T cells of PBMCs from RA patients after 3 months TNF-α blockade treatment was significantly lower than before treatment (2.94 ± 3.21% vs. 7.21 ± 5.64%; p = 0.0001). The disease activity and anti-CCP antibody levels were also significantly reduced after TNF-α blockade treatment. The CD154 expression levels were positively correlated with disease activity index DAS28, and CRP. The post-stimulated CD154 expression percentage of purified CD4+ T cells between baseline and after TNF-α blockade treatment was not significantly different (p = 0.221). Baseline CD154 levels were positively correlated with treatment-induced changes in DAS28 (p = 0.014; r2 = 0.187).
TNF-α blockade treatment significantly decreased the CD154 expression on CD4+ T cells, disease activity and anti-CCP antibody simultaneously in RA patients. However TNF-α blockade did not impair T cell capacity to express CD154 after stimulation. These results suggest that decreased CD154 expression after TNF-α blockade may be due to decreased RA disease activity but not direct inhibition of CD154 responsiveness of T cells.
CD154（通常称为CD40配体）是一种关键的T细胞因子，参与自身免疫发病机制，且在类风湿关节炎（RA）中过度表达。肿瘤坏死因子-α（TNF-α）阻断治疗在RA中具有显著疗效。
研究TNF-α阻断治疗是否能抑制RA中CD154的表达。
收集33例类风湿关节炎患者在TNF-α阻断治疗前及治疗3个月后的血样。对这两个时间点通过标准检测方法测定的临床血清学数据以及通过流式细胞术测定的T细胞CD154表达水平进行统计学分析。
TNF-α阻断治疗3个月后，RA患者外周血单个核细胞（PBMC）中门控CD4⁺T细胞上CD154表达的百分比显著低于治疗前（2.94±3.21%对7.21±5.64%；p = 0.0001）。TNF-α阻断治疗后疾病活动度和抗环瓜氨酸肽（CCP）抗体水平也显著降低。CD154表达水平与疾病活动指数DAS28以及C反应蛋白（CRP）呈正相关。纯化的CD4⁺T细胞在基线和TNF-α阻断治疗后的刺激后CD154表达百分比无显著差异（p = 0.221）。基线CD154水平与治疗诱导的DAS28变化呈正相关（p = 0.014；r² = 0.187）。
TNF-α阻断治疗可使RA患者CD4⁺T细胞上的CD154表达、疾病活动度和抗CCP抗体同时显著降低。然而，TNF-α阻断并未损害T细胞在刺激后表达CD154的能力。这些结果表明，TNF-α阻断后CD154表达降低可能是由于RA疾病活动度降低，而非直接抑制T细胞的CD154反应性。
