Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus ErythematosusReport as inadecuate




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Background-Purpose

A slight increase in the proportion of circulating regulatory T Treg cells has been reported in systemic lupus erythematosus SLE patients taking oral prednisone. The effects of intravenous IV high dose methylprednisolone MP on Tregs have not yet been described, especially in active SLE.

Methods

We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: 1 naïve Treg nTreg FoxP3lowCD45RA+ cells; 2 effector Treg eTreg FoxP3highCD45RA− cells; and 3 non-suppressive FoxP3lowCD45RA− cells non-regulatory Foxp3low T cells. Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP day 0 and the following days day 1, day 2, ±day 3 and ±day 8. The activity of SLE was assessed by the SLEDAI score.

Results

Seventeen patients were included. Following MP infusions, the median range percentage of eTregs significantly increased from 1.62% 0.53–8.43 at day 0 to 2.80% 0.83–14.60 at day 1 p = 0.003 versus day 0, 4.64% 0.50–12.40 at day 2 p = 0.06 versus day 1 and 7.50% 1.02–20.70 at day 3 p = 0.008 versus day 2, and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% 3.20–17.70 at day 0 to 4.74% 1.03–9.72 at day 2 p = 0.005; nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2.

Conclusion

IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE.



Author: Alexis Mathian , Romain Jouenne , Driss Chader, Fleur Cohen-Aubart, Julien Haroche, Jehane Fadlallah, Laetitia Claër, Lucile Mus

Source: http://plos.srce.hr/



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