Researchers from the Shiraz University of Medical Sciences, Iran, unraveled a potential connection between specific regulatory T cells (Tregs) and the formation of inhibitors in patients with severe hemophilia A.

According to the findings recently published in the International Journal of Laboratory Hematology, patients with inhibitors exhibited notably lower levels of CD4+CD25FOXP3+ Tregs than patients without inhibitors and healthy controls.

Moreover, the frequency of CD4+CD25+ T cells was significantly higher in patients with hemophilia A who developed inhibitors compared with those who did not, whereas the levels of these T cells were lower in patients with hemophilia A without inhibitors compared with healthy controls.

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“The clinical significance of the lower proportion of the CD4+CD25FOXP3+ T cell subsets in our hemophilia A patients with inhibitors is obscure. However, considering the positive association between CD4+CD25FOXP3+ T cells and CD4+FOXP3+ populations in our study, it is conceivable that these cells might have regulatory properties in hemophilia A patients with inhibitors, an assumption that needs to be clarified with further comprehensive studies,” the researchers said.

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Furthermore, the researchers found a positive correlation between the percentages of CD4+CD25+ T cells and the levels of inhibitors in patients with hemophilia A.

The researchers conducted a cross-sectional analysis enrolling 32 patients with severe hemophilia A (8 patients with inhibitors and 24 patients without inhibitors). The study included 24 healthy individuals as controls.

Although further studies are required to investigate the underlying mechanisms, this study provides valuable insights into the role of Tregs, in particular FOXP3+ Tregs, in inhibitor formation among patients with severe hemophilia A.

It is worth mentioning that data regarding the role of CD4+CD25FOXP3+ T cells is currently limited; however, existing studies in patients with systemic lupus erythematosus indicate that these cells predominantly resemble Tregs rather than activated T cells, as the study’s authors explained.


Arandi N, Zekavat OR, Shokrgozar N, Shahsavani A, Golmoghaddam H, Kalani M. Altered frequency of FOXP3+ regulatory T cells is associated with development of inhibitors in patients with severe hemophilia A. Int J Lab Hematol. Published online July 24, 2023. doi:10.1111/ijlh.14139