The Expression And Correlation Research Of MDSC,T-lymphocyte Subsets And Cytokines In Peripheral Blood Of Low-risk Myelodysplastic Syndrome Treated By Cyclosporine A And Thalidomide

Objective:This study was designed to investigate the differential expression of myeloid-derived suppressor cells,T-lymphocyte and the related cytokines in the peripheral blood of the low-risk(low-risk and intermediate risk in IPSS Prognosis Score)myelodysplastic syndromes patients before and after the treatment of cyclosporine A and thalidomide,which would reflect the immune status of low-risk MDS patients.Further,we intend to explore the role of MDSC cells in the pathogenesis of MDS.Methods: 19 newly diagnosed,primary,low-risk MDS patients(low-risk and intermediate risk in IPSS Prognosis Score)and 9 healthy individuals in Lanzhou University Second Hospital were enrolled into the study.All of the patients had received treatement of cyclosporine A and thalidomide.The proportions of MDSC,CD4~+T,CD8~+T,Th1 cell,Th2 cell,Th17 cell,Treg cell and CD3~+CD8—IL-10~+ cell in peripheral blood were measured by flow cytometry.The concentration of interferon-gama,interleukin-4,interleukin-17,interleukin-10 and tumor necrosis factor-alpha levels were detected using ELISA.All statistical analyses were performed using SPSS 19.0 software.The Student's t-test was used for statistical comparisons.Bivariate(Pearson)Correlation analysis was uesd for correlation analysis.Results:1.Compared with the normal controls,the proportion of MDSC before treatment was higher(2.35±1.76% vs 0.87±0.19%,P<0.01).The proportion of MDSC decreased after treatment(1.46±0.77% vs 2.35±1.76%,P<0.05).2.Compared with the normal controls,the proportion of CD4~+T before treatment was lower(35.26±3.87% vs 48.72±1.82%,P<0.01)and the proportion of CD8~+T was higher(28.40±5.29% vs 21.53±3.91%,P< 0.05)with a smaller CD4~+T/CD8~+T ratio(1.28±0.28 vs 2.33±0.43,P<0.01).Compared with the samples before treatment,the proportion of CD4~+T was higher(39.80±2.94% vs 35.26±3.87%,P<0.01)and the proportion of CD8~+T was lower(24.18±2.63% vs 28.40±5.29%,P<0.05)with a bigger CD4~+T /CD8~+T ratio(1.66±0.18 vs 2.33±0.43,P<0.01)after treatment.3.Compared with the normal controls,the proportion of Th1 before treatment was higher(13.95±1.42% vs 10.43±0.59%,P<0.01)and the proportion of Th2 was lower(0.78±0.11% vs 0.90±0.05%,P<0.01)with a bigger Th1/Th2 ratio(18.29±3.39 vs 11.59±1.04%,P<0.01)Besides,the proportion of Th17 before treatment was higher(1.89±0.48% vs 0.96±0.18%,P<0.01)and so was the the proportion of Treg(6.80±0.93% vs 5.80±0.99%,P<0.01).Compared with the samples before treatment,the proportion of Th1 decreased(11.4±1.27% vs 13.95±1.42%,P<0.01)and the proportion of Th2 increased(0.88±0.11% vs 0.78±0.11%,P<0.01),with a smaller Th1/Th2 ratio(13.16±1.80 vs 18.29±3.39,P<0.01)after treatment.In addition,the proportion of Th17 and Treg were lower(1.41±0.33% vs 1.89±0.48%,5.35±0.68% vs 6.80±0.93% respectively P<0.01)after treatment.4.Compared with the normal controls,the proportion of CD3~+ CD8—IL-10~+ cell before treatment was higher(5.72±1.30% vs 3.39±0.79%,P<0.01).Compared with the the samples before treatment,the proportion of CD3~+ CD8—IL-10~+ cell decreased(4.72±0.89% vs 5.72±1.30%,P<0.01)after treatment.5.Compared with the normal controls,the level of IFN-gama before treatment was higher(11.16±1.20% vs 6.19±0.97%,P<0.01),the level of IL-4 was lower(19.39±2.64% vs 22.63±2.59%,P<0.05);the level of IL-17 was higher(27.05±1.46% vs 18.89±1.01%,P<0.01);the level of IL-10 was higher(43.33±4.67% vs 4.21±1.30%,P<0.01);the level of TNF-? was higher(29.03±8.75% vs 6.02±1.01%,P<0.01).Compared with the samples before treatment,the level of IFN-gama decreased(8.10±1.06% vs 11.16±1.20%,P<0.01);the level of IL-4 increased(21.12±2.17% vs 19.39±2.64%,P<0.05),the level of IL-17 decreased(21.67±1.52% vs 27.05±1.46%,P<0.01);the level of IL-10 decreased(14.51±2.47% vs 43.33±4.67%,P<0.01)and the level of TNF-? decreased(18.45±1.76% vs 29.03±8.75%,P<0.01)after treatment.6.In the peripheral blood samples before treatment,the proportion of MDSC and the level of hemoglobin were negatively correlated(r=-0.497,P<0.05),the proportion of MDSC and CD4~+T were negatively correlated(r=-0.827,P<0.01),the proportion of MDSC and Th17 were positively correlated(r=0.595,P<0.05),the proportion of MDSC and Treg were highly positively correlated(r=0.724,P<0.01),the proportion of MDSC and CD3~+ CD8—IL-10~+ cell were highly positively correlated(r=0.588,P<0.05),the proportion of MDSC and the level of IL-17 in serum were positively correlated(r=0.498,P<0.05),the proportion of MDSC and the level of IL-10 in serum were positively correlated(r=0.686,P<0.05)and the proportion of MDSC and the level of TNF-? in serum were positively correlated(r=0.581,P<0.05).Conclusions:1.The proportion of MDSC in the peripheral blood of low-risk MDS patients was significantly higher than that in normal controls,which was negatively correlated with the level of hemoglobin.2.The immunoligical abnormality in low-risk MDS patients included:the imbalanced CD4~+T/ CD8~+T ratio,higher level of Th1,Th17 and Treg,imbalanced Th1/ Th2 ratio and disorder of IFN-?,IL-4,IL-17,IL-10 and TNF-?,which can be improved by cyclosporine A and thalidomide.3.The proportion of MDSC and CD4~+T in the peripheral blood of low-risk MDS patients were negatively correlated;the proportion of MDSC and Th17,Treg were positively correlated;the proportion of MDSC and the level of IL-10,TNF-? in serum were positively correlated.All these indicated that MDSC cells were associated with the disorder of T-lymphocyte subsets.We infer that MDSC cells may play an important role in the immunological disorders of MDS and they may become the potential therapy target for MDS.