Circulating myeloid-derived suppressor cells predict disease activity and treatment response in patients with immune thrombocytopenia

Abstract

Immune thrombocytopenia (ITP) is a disease characterized by isolated thrombocytopenia. Abnormal effector T cell activation is an important mechanism in the pathogenesis of ITP. Regulatory T cells (Treg) have a strong immunosuppressive function for T cell activation and their importance in the pathophysiology and clinical treatment of ITP has been confirmed. Myeloid-derived suppressor cells (MDSCs) are other immunosuppressive cells, which can also suppress T cell activation by secreting arginase, iNOS and ROS, and are essential for Treg cells’ differentiation and maturation. Therefore, we speculate that MDSCs might also be involved in the immune-dysregulation mechanism of ITP. In this study, we tested MDSCs and Treg cells in peripheral blood samples of twenty-five ITP patients and ten healthy donors. We found that MDSCs and Treg cells decreased simultaneously in active ITP patients. Relapsed ITP patients showed lower MDSCs levels compared with new patients. All patients received immunosuppressive treatment including dexamethasone alone or in combination with intravenous immune globulin. We found that MDSCs’ level after treatment correlated with platelet recovery. Our study is the first that focused on MDSCs’ role in ITP. Based on our results, we concluded that circulating MDSCs could predict disease activity and treatment response in ITP patients. This preliminary conclusion indicates a substantial significance of MDSCs in the pathophysiology and clinical treatment of ITP, which deserves further investigation.

Distinct alterations of CD68+CD163+ M2-like macrophages and myeloid-derived suppressor cells in newly diagnosed primary immune thrombocytopenia with or without CR after high-dose dexamethasone treatment

“…MDSCs are uniformly characterized by the co-expression of myeloid-cell lineage differentiation antigen GR1 and CD11b [ 22 , 23 ] in mice, but cell surface markers defining human MDSCs have not yet to be confirmed [ 24 – 26 ]. CD11b + CD33 + HLA-DR − cells sharing multiple MDSCs features were recently identified in ITP patients [ 6 , 7 ]. M2 macrophages are often identified based on the expression patterns of a set of diverse markers.…”

“…MDSCs could expand under pathological conditions including multiple sclerosis [ 28 ], rheumatoid arthritis [ 29 , 30 ] and autoimmune hepatitis [ 31 ]. Recently, studies have shown that circulating MDSCs were reduced in ITP patients [ 6 , 7 ]. In the present study, accumulation of MDSCs but not the M2-like macrophages was observed in ITP patients.…”

“…Clinical investigations for the pathogenesis of ITP have been largely focused on the aberrations related to adaptive immunity including platelet autoantibodies [ 4 ], T cell clonality and T helper differentiation [ 5 ]. Recently, the role of innate immunity and myeloid-derived immune modulator cells have been recognized in the pathogenesis of ITP [ 6 , 7 ].…”

“…Recently, studies have identified the pathogenic role of MDSCs in ITP. Impaired MDSCs have been implicated in the pathogenesis of ITP [ 6 ] via direct inhibition of T cell activation or the indirect induction of regulatory T cells (Tregs), which could also act as a prognostic marker for treatment responses in ITP [ 7 ]. As another important myeloid-derived cell compartment, macrophages have been implicated to be active in the perturbation of immune tolerance in ITP.…”

Immune thrombocytopenia induces autophagy and suppresses apoptosis in megakaryocytes

“…Investigations regarding the mechanism of autoimmune diseases have focused mainly on the destruction of platelets, decrease in platelet production and T lymphocyte immune imbalance (3,14). Studies of the survival of megakaryocytes in ITP patients are rare and few studies have investigated the role of autophagy in ITP.…”