Deficient or abundant but unable to fight? Estimation of circulating FoxP3+ T regulatory cells and their counteracting FoxP3- in rheumatoid arthritis and correlation with disease activity
Deficient or abundant but unable to fight? Estimation of circulating FoxP3+ T regulatory cells and their counteracting FoxP3- in rheumatoid arthritis and correlation with disease activity
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DOI：
10.1016/j.ejr.2013.03.005
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发表时间：
2013-10-01
影响因子：
0.9
通讯作者：
Abo-Shady, Rania A.
中科院分区：
文献类型：
--
作者：
Abaza, Nouran;EL-Kabarity, Rania H.;Abo-Shady, Rania A.
工作目标：风湿病学家对类风湿性关节炎（RA）中T调节细胞（Tlymphocyte，Tlymphocyte）四分卫的持续炎症和复发活动感兴趣。最具特异性的标记是叉头框P3（FoxP 3），表示FoxP 3（+）细胞作为抑制因子，而FoxP 3（-）作为效应因子。本研究评估外周血（PB）的CD 4（+）CD 25（+）T细胞亚群分布根据FoxP 3表达在RA，以更好地了解其在pathogenicity.Patients和方法的作用：在我们的观察性横断面研究PB T细胞从40例RA患者和20个年龄和性别匹配的健康对照组（HC）的特点和定量流式细胞术。通过DAS 28评估疾病活动性。患者分为：RA活动期组（ARA）和RA缓解期组（RRA）。RRA、ARA和HC患者的CD 4（+）CD 25（+）FoxP 3（+）T细胞亚群明显高于正常对照组（平均值分别为153.25 +/- 6.29、136.3 +/- 3.27和97.25 +/- 6.25），具有统计学上高度显著的差异（F = 553.13，p < 0.001）。与HC相比，RRA中CD 4（+）CD 25（+）FoxP 3（-）增加3倍，ARA中增加4倍，RRA中CD 4（+）CD 25（+）FoxP 3（+）增加1.6倍，ARA中增加1.5倍。因此，FoxP 3（-）/FoxP 3（+）细胞的比例从HC中的1：3改变为RRA中的2：3和ARA中的1：1。CD 4（+）CD 25（+）FoxP 3（+）与疾病活动性评分DAS 28呈显著负相关结论：RA患者CD 4（+）CD 25（+）FoxP 3（+）和CD 4（+）CD 25（+）FoxP 3（-）均升高，但两者的平衡更为重要;具有效应子功能的大量FoxP 3（-）细胞比抑制性FoxP 3（+）细胞占优势。这种不平衡与RA的存在和活动有关。增强FoxP 3的表达可能是治疗RA的一个潜在靶点。（C）2013年由Elsevier B. V.代表埃及关节疾病和关节炎协会制作和主办。
Aim of the work: Persistent inflammation and recurring activity in rheumatoid arthritis (RA) daring a quarterback of T regulatory cells (Tregs) intrigued rheumatologists. Tregs' most specific marker is the forkhead box P3 (FoxP3) denoting FoxP3(+) cells as suppressors whereas FoxP3(-) as effectors. This study evaluates subset distribution of peripheral blood (PB) CD4(+) CD25(+) Tregs according to FoxP3 expression in RA to better understand its role in pathogenesis.Patients and methods: In our observational cross-sectional study PB Tregs from 40 RA patients and 20 age and sex matched healthy controls (HC) were characterized and quantified by flow cytometry. Disease activity was evaluated by DAS28. Patients were divided into: active RA group (ARA) and remission RA group (RRA).Results: Significantly higher CD4(+) CD25(+) FoxP3(+) Tregs were found on comparing RRA, ARA patients and HC (mean 153.25 +/- 6.29, 136.3 +/- 3.27 and 97.25 +/- 6.25, respectively) with a statistically highly significant difference (F = 553.13, p < 0.001). CD4(+) CD25(+) FoxP3(-) increased 3-folds in RRA and 4-folds in ARA compared to HC and CD4(+) CD25(+) FoxP3(+) increased 1.6-folds in RRA and 1.5-folds in ARA. Thus the ratio of FoxP3(-)/FoxP3(+) cells is altered from 1:3 in HC to2:3 in RRA and 1:1 in ARA. CD4(+) CD25(+) FoxP3(+) had a highly significant negative correlation with disease activity score DAS28 (r = -0.86, p < 0.001).Conclusion: Though CD4(+) CD25(+) FoxP3(+) and CD4(+) CD25(+) FoxP3(-) are both increased in RA, their balance is more important; abundant FoxP3(-) cells with effector function have the upper hand over suppressive FoxP3(+) cells. This imbalance relates to RA presence and activity. Reinforcing FoxP3 expression might be a good potential therapeutic target in RA. (C)2013 Production and hosting by Elsevier B.V. on behalf of Egyptian Society for Joint Diseases and Arthritis.