کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5527915 | 1547893 | 2017 | 12 صفحه PDF | دانلود رایگان |
- Higher peripheral Treg number in low risk patients with MDS compared to high risk.
- Treg suppression activity is impaired in MDS patients.
- Increased in vitro cytokine production from MDS patients' T cells after 12 months.
- Negative correlation between IRF-1 and Foxp3 on initial evaluation.
- Results suggest a progressive immune hyper activity following MDS evolution.
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 (T0) 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, â4, â6, â10, â17, TNFα and IFNγ 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 (T0 = 5.62 ± 2.84 Ã 105 vs T12 = 4.87 ± 2.62 Ã 105; 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 Ã 105) versus high risk group (2.6 ± 1.2 Ã 105, p = 0.03). Treg suppression activity was impaired on T0 and T12.Cytokine production and IRF-1 expression were increased on T12. The correlation between IRF-1 and FoxP3 was negative (r2 = 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.
Journal: Leukemia Research - Volume 55, April 2017, Pages 6-17