Glucocorticoid treatment in patients with newly diagnosed immune thrombocytopenia switches CD14 ⁺⁺CD16 ⁺ intermediate monocytes from a pro-inflammatory to an anti-inflammatory phenotype

Immune thrombocytopenia (ITP) is thought to result from an aberrant adaptive autoimmune response, involving autoantibodies, B and T lymphocytes, directed at platelets and megakaryocytes. Previous reports have demonstrated skewed CD4+ T helper subset distribution and enhanced production of pro-inflammatory cytokines such as IL-17A and IFN-γ. The role of monocytes in ITP is less widely described, but innate immune cells have a role in shaping CD4+ T cell phenotypes. Glucocorticoids (GCs) are commonly used for first line ITP treatment and modulate a broad range of immune cells including T cells and monocytes. Using multiparameter flow cytometry analysis, we demonstrate expansion of intermediate monocytes (CD14++CD16+) in untreated newly diagnosed, ITP patients, with these cells displaying a pro-inflammatory phenotype, characterised by enhanced expression of CD64 and CD80. After 2 weeks of prednisolone treatment (1mg/kg daily), the proportion of intermediate monocytes reduced, with enhanced expression of the anti-inflammatory markers CD206 and CD163. Healthy control monocytes were distinctly different from those from ITP patients before and following GC-treatment. Furthermore, the GC-induced phenotype was not observed in patients with chronic ITP receiving thrombopoietin receptor agonists. These data suggest a role of monocytes in ITP pathogenesis and clinical response to GC-therapy.