Distinct distributions of lymphocyte subsets in myelodysplastic syndrome correlate with risk stratification Free

Introduction Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal disorders affecting hematopoietic stem cells. The pathogenesis of MDS is highly complex, with dysregulated DNA demethylation being one of the major underlying mechanisms. Immune dysregulation has been demonstrated to play a role in MDS, including abnormalities of lymphocyte subsets. Previous studies have not elucidated the differences in specific lymphocyte subpopulations. This study aims to systematically present the distribution of lymphocyte subsets in bone marrow and peripheral blood from patients with MDS based on the risk stratification.

Methods This cohort study was conducted including 54 newly diagnosed MDS patients at Qilu Hospital of Shandong University. Seventeen healthy donors were enrolled as controls. Patients were stratified according to the Revised International Prognostic Scoring System (IPSS-R). IPSS-R risk categories “very low” and “low” were considered as LR-MDS, whereas “intermediate”, “high” and “very high” were considered as HR-MDS. Multi-parameter flow cytometry (MFC) was employed to quantify the specific lymphocyte subsets in bone marrow and peripheral blood, including T helper 1 (Th1)/Th2/Th17/effector T cells, follicular helper T (Tfh) cells, peripheral helper T (Tph) cells, suppressor T lymphocytes, total B cells, memory B cells and natural killer (NK) cells.

Results Our results showed that, compared with the control group, LR-MDS patients exhibited a significantly increased proportion of Tfh cells (P = 0.017) but significantly decreased proportions of Tph cells (P = 0.013) and total B cells (P = 0.012) in the bone marrow. Whereas the proportion of memory B cells was significantly increased (P = 0.003) in the peripheral blood. Patients with HR-MDS displayed significantly increased proportions of suppressor T lymphocytes (P = 0.023) and Tfh cells (P = 0.007) and NK cells (P = 0.015) in the bone marrow. Moreover, the proportion of Tph cells in HR-MDS was also significantly lower in both the bone marrow (P= 0.006) and peripheral blood (P = 0.006). While, compared with controls, no significant differences were observed in the proportions of Th1, Th2, Th17, or effector T cells within peripheral blood and bone marrow from either LR-MDS or HR-MDS patients.

Conclusion Our finding showed that MDS patients exhibit significant immune dysregulation, characterized by elevated proportions of Tfh cells, NK cells, and naïve regulatory T cells, alongside reduced proportions of Tph cells and B cells. Notably, the lymphocytes abnormalities were correlated with MDS risk stratification. Crucially, the precise distribution of lymphocyte subsets indicates the presence of a divergent immune milieu between the LR-MDS and HR-MDS. Our findings revealed a valuable framework for evaluating disease progression and monitoring changes in immune function in MDS.