Contributions
Abstract: PB2079
Type: Publication Only
Background
Assuming that the immune system plays an active role in pathogenesis of myelodysplastic syndrome (MDS), it is expected that certain immune responses, namely, the number of regulatory T‑cells (Treg cells), can be used as prognostic criteria. Participation of Tregs in pathogenesis of MDS can partly explain the link between MDS and autoimmune disorders, as well as tumor transformation.
Aims
Estimate the number of regulatory T‑cells and level of expression of FOXP3 molecule isoforms differing by the exon-2 in peripheral blood of patients with MDS at early and late stages.
Methods
The evaluation was performed on peripheral blood mononuclear cells (PBMC). Various fluorochrome-labeled monoclonal antibodies (eBioscience) were used. As a negative control for establishing of gates for FOXP3+ cells, we used a non-expressing FOXP3 molecules subpopulation of CD3-negative cells.
Results
55 patients with MDS (WHO 2008) were examined. Patients with low and intermediate-1 risk of IPSS were included in the early-stage MDS group (E‑MDS), and intermediate-2 and high-risk IPSS patients were included into the late stage MDS group (L‑MDS). The obtained values for E‑MDS and L‑MDS groups did not differ significantly. When compared with the age control group, the absolute number of leukocytes, lymphocytes, and CD4+ T‑cells was found to be decreased, which is typical for MDS. In both groups, more than two-fold decrease in the absolute number of Tregs was registered. Treg decrease was proportional to the degree of leukopenia and somewhat more pronounced than decrease level of the number of lymphocytes and all CD4+ T‑cells, which is due to decrease of the proportion of Tregs among CD4+ T‑cells. The decrease of Treg percentage was statistically significant in the E‑MDS group only, which suggests a higher probability of autoimmune disorders in this group. A significant decrease of the number of Tregs was shown, both expressing the complete FOXP3 molecule (FOXP3‑FL Treg) and expressing only the FOXP3 molecule without exon-2 (FOXP3D2 Treg). Decrease of the number of FOXP3D Treg in peripheral blood was more pronounced than the decrease of FOXP3‑FL Treg, which is due to a significant increase of the relative proportion of the latter. Presumably, the Treg functional activity in MDS is attenuated due to decrease of the proportion of FOXP3D2 Treg, known to be the most active suppressor of the immune response.
Conclusion
The data obtained shows a functionally intermediate role of Treg in MDS compared to inflammatory (autoimmune) diseases and the norm, and its opposite role in malignant neoplasms. The basic mechanisms of MDS pathogenesis, including Treg function, need further study, which may lead to subdivision of different diseases with a distinctive clinical picture and outcome.
Session topic: 9. Myelodysplastic syndromes – Biology & Translational Research
Keyword(s): MDS, Myelodysplasia, T cell
Abstract: PB2079
Type: Publication Only
Background
Assuming that the immune system plays an active role in pathogenesis of myelodysplastic syndrome (MDS), it is expected that certain immune responses, namely, the number of regulatory T‑cells (Treg cells), can be used as prognostic criteria. Participation of Tregs in pathogenesis of MDS can partly explain the link between MDS and autoimmune disorders, as well as tumor transformation.
Aims
Estimate the number of regulatory T‑cells and level of expression of FOXP3 molecule isoforms differing by the exon-2 in peripheral blood of patients with MDS at early and late stages.
Methods
The evaluation was performed on peripheral blood mononuclear cells (PBMC). Various fluorochrome-labeled monoclonal antibodies (eBioscience) were used. As a negative control for establishing of gates for FOXP3+ cells, we used a non-expressing FOXP3 molecules subpopulation of CD3-negative cells.
Results
55 patients with MDS (WHO 2008) were examined. Patients with low and intermediate-1 risk of IPSS were included in the early-stage MDS group (E‑MDS), and intermediate-2 and high-risk IPSS patients were included into the late stage MDS group (L‑MDS). The obtained values for E‑MDS and L‑MDS groups did not differ significantly. When compared with the age control group, the absolute number of leukocytes, lymphocytes, and CD4+ T‑cells was found to be decreased, which is typical for MDS. In both groups, more than two-fold decrease in the absolute number of Tregs was registered. Treg decrease was proportional to the degree of leukopenia and somewhat more pronounced than decrease level of the number of lymphocytes and all CD4+ T‑cells, which is due to decrease of the proportion of Tregs among CD4+ T‑cells. The decrease of Treg percentage was statistically significant in the E‑MDS group only, which suggests a higher probability of autoimmune disorders in this group. A significant decrease of the number of Tregs was shown, both expressing the complete FOXP3 molecule (FOXP3‑FL Treg) and expressing only the FOXP3 molecule without exon-2 (FOXP3D2 Treg). Decrease of the number of FOXP3D Treg in peripheral blood was more pronounced than the decrease of FOXP3‑FL Treg, which is due to a significant increase of the relative proportion of the latter. Presumably, the Treg functional activity in MDS is attenuated due to decrease of the proportion of FOXP3D2 Treg, known to be the most active suppressor of the immune response.
Conclusion
The data obtained shows a functionally intermediate role of Treg in MDS compared to inflammatory (autoimmune) diseases and the norm, and its opposite role in malignant neoplasms. The basic mechanisms of MDS pathogenesis, including Treg function, need further study, which may lead to subdivision of different diseases with a distinctive clinical picture and outcome.
Session topic: 9. Myelodysplastic syndromes – Biology & Translational Research
Keyword(s): MDS, Myelodysplasia, T cell