Erythropoietin administration is associated with improved T-cell properties in patients with myelodysplastic...

The immune system is impaired in myelodysplastic syndromes (MDS) and plays a role in the pathogenesis of the disease. Here we show effects of recombinant human erythropoietin (rHuEPO) on T cell (CD4⁺, CD8⁺ and CD4⁺CD25⁺) number and function in MDS patients. Healthy (20 subjects), MDS patients without rHuEPO treatment ('MDS', 13), and MDS patients treated with rHuEPO ('MDS+EPO', 17) were examined. CD4⁺ and CD8⁺ T cell numbers were reduced and increased respectively in MDS compared to healthy subjects. EPO treatment normalized these levels. CD4⁺CD25⁺ cell numbers, lower in MDS, were normalized in MDS+EPO. In vitro activation of CD4⁺ and CD8⁺ cells with phytohemagglutinin as measured by CD69 expression, demonstrated a 7.2 fold increase in CD4⁺ activation vs 13.6 fold for MDS and MDS+EPO respectively (p=0.004); and 10.2 fold (MDS) vs 18.6 fold (MDS+EPO, p<0.003) for CD8⁺ T cells. Expression of the co-stimulatory marker CD28, decreased in CD4⁺ and CD8⁺ T cells in MDS, was normalized in MDS+EPO CD4⁺ T cells. Subgroup analysis of milder disease (WHO RA and RARS) and more advanced disease revealed no difference in CD4⁺ and CD8⁺ T cell numbers. However, the activation of these cells in the RA/RARS subgroup was impaired in EPO-untreated and enhanced in EPO-treated MDS patients. Our data suggest that EPO treatment improves immune abnormalities in MDS and may depend on disease severity.