Low-Dose Prednisolone Therapy before Pregnancy Positively Impacts the Increase of Granulocytic Myeloid-Derived Suppressor Cells Relative Monocytic MDSCs, Compared to Lymphocyte Immunotherapy, in Women with Recurrent Miscarriages

Abstract

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that play a prominent role in maintaining immune tolerance. Despite considerable advances in reproductive immunology, current therapeutic regimens have failed provide a definitive solution for affected women, underscoring the imperative for continued investigation into the underlying mechanisms and novel intervention strategies. OBJECTIVE: To evaluate the effects of low-dose prednisolone therapy and lymphocyte immunotherapy (LIT) on MDSC subsets in women with recurrent miscarriage (RM) before pregnancy. METHODS: 100 women with RM were divided into two groups: a short-term low-dose prednisolone therapy group (n=50), and an LIT group (n=50). Blood samples were taken before and after the interventions and analyzed using flow cytometry. Specifically, we identified three MDSC subsets based on their surface markers: CD33+CD66+, CD15+CD66+, and CD14+CD66+ cells. RESULTS: LIT treatment significantly reduced CD33+CD66+ MDSCs (P=0.036). There were no significant differences in MDSC subsets before intervention, while prednisolone therapy increased granulocytic MDSCs (GR-MDSCs) compared to monocytic MDSCs (MO-MDSCs) in women with RM (P=0.046). In the LIT group, the decrease in the percentage of GR-MDSCs following treatment resulted in a significantly lower percentage of these cells compared to MO-MDSCs (P=0.0002). CONCLUSION: Prednisolone increases the GR-MDSC to MO-MDSC ratio, while LIT decreases GR-MDSCs, shifting the balance toward MO-MDSCs. Both approaches have immunomodulatory effects in the pre-conception period, and they affect MDSCs as well as other immune cells that may be important for improving implantation success in women with RM.