Unveiling the role of circulating monocyte-macrophage polarization state and PD-L1/PD-L2 expression in newly diagnosed pediatric ITP.

Abstract

Background: Immune thrombocytopenia (ITP) is an immune-mediated disorder characterized by decreased platelet count resulting from immune dysregulation and altered cellular immune responses. This study aimed to evaluate monocyte-macrophage polarization patterns and the expression of immune checkpoint molecules CD273 (PD-L2) and CD274 (PD-L1) in patients with ITP and explore their association with hematological parameters and response to corticosteroid therapy.

Methods: This case-control study compared patients with primary ITP and healthy controls. Hematological indices were assessed using complete blood counts, and monocyte-macrophage subsets including M1-like and M2-like populations and their subtypes (M2a, M2b, and M2c), along with CD273 and CD274 expression were analyzed by flow cytometry.

Results: Patients with ITP showed significantly lower hemoglobin levels, platelet counts, and lymphocyte counts, with higher mean platelet volume (MPV) and platelet distribution width (PDW) compared with controls. A marked increase in M1-like monocyte-macrophages with a concomitant reduction in total M2-like cells was observed in patients with ITP. Within M2 subsets, M2a-like cells were increased, whereas M2b-like and M2c-like subsets were decreased. Expression of CD273 and CD274 were reduced on M1-like cells, and CD273 expression was significantly decreased on M1-like and M2a-like subsets only, with non-significant trends in M2b-like cells. Non-responders to corticosteroid therapy demonstrated higher M1 polarization, increased M2a levels, reduced M2b and M2c subsets, and lower CD273 expression among M1 and M2a compared with responders. Significant correlations were identified between macrophage-like subsets and platelet count, hemoglobin, MPV, and PDW.

Conclusion: These findings suggested that a pro-inflammatory M1-like polarization shift combined with an impaired dual PD-L1/PD-L2 checkpoint expression on M2b-like macrophages are significantly correlated with platelet indices and collectively contribute to ITP immunopathogenesis and treatment response, supporting macrophage polarization as a promising immunomodulatory target.