Altered frequency of FOXP3+ regulatory T cells is associated with development of inhibitors in patients with severe hemophilia A

Abstract

AbstractIntroductionThe development of anti‐factor VIII (FVIII) antibodies or “inhibitors” is a major complication following FVIII replacement therapy in patients with severe hemophilia A (HA), rendering the treatment inefficient. Data on the role of regulatory T cells (Tregs) in inhibitor formation in these patients are rare. Herein, we aimed to investigate whether a difference in the FOXP3+ Tregs is linked to the formation of the inhibitors in severe HA patients.MethodsIn this cross‐sectional study, 32 patients with severe HA (8 patients with inhibitors and 24 without inhibitors) and 24 healthy controls were enrolled. The frequency of FOXP3+ Tregs was determined using multicolor flow cytometry method.ResultsOur results showed that the median level of CD4+CD25+FOXP3+ Tregs did not significantly differ between HA patients and healthy controls and between HA patients with and without inhibitors (P > 0.05). However, patients with inhibitors had significantly lower amounts of CD4+CD25−FOXP3+ Tregs compared to those without inhibitors as well as healthy controls (*P = 0.012 and *P = 0.004, respectively). The frequency of CD4+CD25+ T cells was significantly higher in HA patients who developed inhibitors compared to the inhibitor‐negative ones whereas they were lower in inhibitor‐negative patients compared to the healthy controls (*P = 0.013 and *P = *0.029, respectively). The percentages of CD4+CD25+ T cells were positively correlated with the levels of inhibitors in HA patients (r = 0.45, *P = 0.021).ConclusionOur data demonstrated for the first time that the CD4+CD25−FOXP3+ Tregs might be implicated in the prevention of inhibitor formation in severe HA patients.