ABSTRACT
CD4+-, CD25+, Foxp3+ regulatory T cells [Tregs] play a central role in maintaining immune tolerance and their expansion in malignant disease and MDS may lead to the suppression of host anti tumor responses and hence disease progression. Therapeutic application of Tregs in treating cancer and autoimmune diseases is now extensively investigated. Our aim is to investigate the clinical significance of Tregs in MDS correlating it to some laboratory findings. This study was carried out on 35 subjects. 25 patients with confirmed diagnosis of primary MDS [group 1] and 10 healthy controls [group 2], their ages were 55 +/- 11.5. and 53 +/- 10.6 respectively, patients were classified according to the WHO classification into 5 [20%] R.A. with or without ringed sideroblasts, 7[28%] RCMD, 10[40%] RAEB, 3[12%] CMML. Stained Leishman and Prussian blue [peri's reaction] blood and BM smears were examined to diagnose MDS then Conventional cytogenetic analysis and banding using Giemsa stain after BM cells culture on RBMI media for 72 h.Flowcytometric analysis of CD4+, CD25+, foxp3+ regulatory T cells [Tregs] in whole blood was done using FITC anti CD4 and PE anti CD 25 for surface staining then after a permibilization step intracellular staining of Foxp3 using PE anti-human Foxp3 was done to determine the Tregs percent. The mean percent of tregs in RA-RARS group was 1.4% +/- 0.7 which was not statistically significant in comparison to control 1.3 +/- 0.5. In RCMD group tregs were 3.3% +/- 2.1 which was not statistically significant in comparison to control. RAEB group showed tregs percent of 5.4% +/- 1.4 and the difference was significant CMML group showed treg percent of 4.6% +/- 1.16 the difference was statistically significant. There was a significant difference when comparing mean percent of tregs in low risk group with those of intermediate and high risk groups. We also found that cases of MDS with more than 5% blasts had significantly higher tregs percent [5.1 +/- l.l] compared to cases of MDS with less than 5% blasts [2.2 +/- 1.3] in B.M. We found no significant correlation between platlet count and Tregs or WBCs count and Tregs but a highly significant positive correlation was present between presence of more than 5% blasts and Tregs. When correlating Tregs with the risk level of our patients there was significant positive correlation between percent of Tregs and the intermediate risk level and a highly significant positive correlation between percent of Tregs and high risk level. The clinical significance of Tregs and its role in MDS varies from disease stage to another, Tregs expansion is evident in RAEB and CMML. while it is not so in RA/RARS or RCMD suggesting its contribution in development of high risk MDS and disease progression to acute leukemia. Attempts to decrease its number or function may will be one of the effective treatment options. Extensive studies on large number of MDS patients are needed to clear the significance of Tregs in each disease subtype and its possible application as a new treatment modality in MDS