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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• 作者：Nouran Abaza ; Rania H. EL-kabarity ; Rania A. Abo-Shady
• 关键词：T regulatory cells ; Rheumatoid arthritis ; FoxP3
• 刊名：The Egyptian Rheumatologist
• 出版年：2013
• 出版时间：October, 2013
• 年：2013
• 卷：35
• 期：4
• 页码：185-192
• 全文大小：892 K

文摘

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 ¡À 6.29, 136.3 ¡À 3.27 and 97.25 ¡À 6.25, respectively) with a statistically highly significant difference (m>Fm> = 553.13, m>pm> < 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 to 2:3 in RRA and 1:1 in ARA. CD4⁺CD25⁺FoxP3⁺ had a highly significant negative correlation with disease activity score DAS28 (m>rm> = ?0.86, m>pm> < 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.