Differential expression of miR-128 in memory T cells of patients with severe hemophilia A with and without inhibitors.

BACKGROUND

Inhibitor development occurs in ∼30% of persons with severe hemophilia A treated with factor (F)VIII replacement products, but the real mechanism of the development is poorly known. miR-128 is a crucial regulator of immune responses, and it is implicated in the pathobiology of various autoimmune disorders.

OBJECTIVES

To investigate the expression of miR-128 in peripheral blood mononuclear cells (PBMCs) and CD4+ naïve and memory T cells of patients with severe hemophilia A with and without inhibitors.

METHODS

Forty-five patients with severe hemophilia A, >50 exposures to FVIII and with persistent (n = 9), transient (n = 10), or no inhibitor (n = 26) were enrolled. The whole blood was drawn to isolate PBMCs and then CD4+ naïve and memory T cells. Total RNA was extracted, and levels of miR-128 were evaluated in PBMCs, naïve T cells, and memory T cells by quantitative polymerase chain reaction. Analysis of covariance test was used to compare the expression of miR-128 in different inhibitor conditions.

RESULTS

A statistically significant increase in miR-128 levels in PBMCs (1.5-fold change; P = .027) and memory T cells (2.6-fold change; P = .015) was found in patients with (persistent and transient) inhibitors compared with patients without inhibitors. In particular, a higher expression of miR-128 in memory T cells (3.8-fold change; P = .022) was found in patients with a persistent inhibitor compared with patients without inhibitors.

CONCLUSION

The present study indicates an overexpression of miR-128 in memory T cells of persons with severe hemophilia A developing inhibitors, likely regulating the expression of key genes in T cell differentiation.