Increase of IRF-1 gene expression and impairment of T regulatory cells suppression activity on patients with myelodysplastic syndrome: A longitudinal one-year study

Studies have demonstrated that abnormalities in interferon regulatory factor-1 (IRF-1) expression might develop myelodysplastic syndromes (MDS). IRF-1 was described as modulator of T regulatory (Treg) cells by suppressing Foxp3 on mice. We aimed to determine the role of Treg and IRF-1 in MDS. Thirty-eight MDS patients fulfilling WHO criteria and classified according to risk scores were evaluated at time 0 (TO) and after 12 months (T12) for: Treg suppression activity in coculture with T effector (Teff) cells; IRF-1 and Foxp3 genetic expression by qRT-PCR; IL-2, 4, 6, 10, 17, TNF alpha. and IFN gamma production by Cytometric Bead Array. No differences in Foxp3 expression (T0 = 0.06 +/- 0.06 vs T12 = 0.06 +/- 0.12, p = 0.5), Treg number (TO = 5.62 +/- 2.84 x 10(5) vs T12 =4.87 +/- 2.62 x 10(5); p = 0.3) and Teff percentage (T0=16.8 +/- 9.56% vs T12 =13.1 +/- 6.3%; p = 0.06) were observed on T12. Low risk MDS patients showed a higher number of Treg (5.2 +/- 2.6 x 10(5)) versus high risk group (2.6 +/- 1.2 x 10(5), p = 0.03). Treg suppression activity was impaired on TO and T12.Cytokine production and IRF-1 expression were increased on T12. The correlation between IRF-1 and FoxP3 was negative (r(2) = 0.317, p = 0.045) on T0. These results suggest a hyper activity of the immune system, probably secondary to Treg suppression activity impairment. This state may induce the loss of tolerance culminating in the proliferation of MDS clones. (C) 2017 Elsevier Ltd. All rights reserved.