Dige Anders, Hvas Christian Lodberg, Deleuran Bent, Kelsen Jens, Bendix-Struve Mia, Dahlerup Jens Frederik, Agnholt Jørgen
Department of Medicine V (Hepatology and Gastroenterology), Gastro-Immuno Research Laboratory (GIRL), Aarhus University Hospital, Denmark.
Scand J Gastroenterol. 2011 Oct;46(10):1206-14. doi: 10.3109/00365521.2011.603157. Epub 2011 Jul 27.
Anti-TNF-α antibodies has been suggested to modulate regulatory T cell (Treg) percentages in rheumatoid arthritis, but results from studies of Crohn's disease (CD) are conflicting. We investigated dynamic changes of circulating Tregs in CD during treatment with the anti-TNF-α-antibody adalimumab (Humira®, Abbott Laboratories A/S, Emdrupvej 28C, DK-2100 Copenhagen).
Blood samples from 26 CD patients were analysed using flow cytometry before and 1 and 26 weeks after initiation of adalimumab treatment to determine the percentage of Tregs among CD4+ T cells.
In spite of a significant decline in disease activity scores and biochemical markers of inflammation, during the first week of treatment, we did not observe early modulating effects of adalimumab on Treg percentages. However, we found a long-term increase in Treg percentages in responders who had low Treg percentages (<5%) at baseline (p = 0.04). Treg percentage was inversely associated with disease activity (CD activity index or CDAI) (Spearman's rank correlation, ρ = -0.47, p = 0.02). High Treg percentages among CD4+ T cells at baseline predicted clinical response to adalimumab.
Adalimumab treatment did not induce early modulatory effects on Treg percentage, even in responders. This finding suggests that adalimumab does not have a direct or selective effect on Tregs. However, Treg percentage was associated with disease activity and high Treg percentage predicted response to adalimumab.
抗TNF-α抗体已被认为可调节类风湿性关节炎中调节性T细胞(Treg)的百分比,但克罗恩病(CD)的研究结果存在矛盾。我们研究了使用抗TNF-α抗体阿达木单抗(修美乐®,雅培实验室A/S,埃姆德鲁普韦28C,丹麦哥本哈根DK-2100)治疗期间CD患者循环Treg的动态变化。
对26例CD患者在开始阿达木单抗治疗前、治疗1周和26周后采集的血样进行流式细胞术分析,以确定CD4+T细胞中Treg的百分比。
尽管疾病活动评分和炎症生化标志物显著下降,但在治疗的第一周,我们未观察到阿达木单抗对Treg百分比的早期调节作用。然而,我们发现基线时Treg百分比低(<5%)的反应者中Treg百分比长期增加(p = 0.04)。Treg百分比与疾病活动(CD活动指数或CDAI)呈负相关(Spearman等级相关,ρ = -0.47,p = 0.02)。基线时CD4+T细胞中高Treg百分比可预测对阿达木单抗的临床反应。
即使在反应者中,阿达木单抗治疗也未对Treg百分比产生早期调节作用。这一发现表明阿达木单抗对Treg没有直接或选择性作用。然而,Treg百分比与疾病活动相关,高Treg百分比可预测对阿达木单抗的反应。