Study of the Serum Immunoglobulin and Cell-Mediated Immunity in Patients with Congenital Severe Hemophilia.

BACKGROUND

It has been shown that a close relationship exists between the immune system and coagulation cascade. Hemophilia A is an X-linked, recessive bleeding disorder caused by deficiency of functional plasma clotting factor VIII that is classically treated with factor VIII replacement therapy. Despite this, some patients produce inhibitors or antibodies against epitopes of infused factor VIII, indicating the activation of the adaptive immune system. The aim of this study was to evaluate the change in the T cell frequency and serum immunoglobulin level in patients with congenital hemophilia A, especially those who produce inhibitors against factor VIII.

METHODS

This is a cross-sectional, case-control study on congenital hemophilia A patients with severe factor VIII deficiency. Twenty-eight hemophilia A male patients were randomly selected along with twenty age-matched healthy males, as the control group. Serum immunoglobulin concentration was measured by nephelometry (for IgG, IgA and IgM) and enzyme-linked immunosorbent assay (ELISA) (for IgE) and the frequency of CD4+ and CD8+ T cells were calculated using a flow cytometry method.

RESULTS

Serum IgG was significantly higher in hemophilic patients compared to controls (14.35 ± 3.60, vs. 12.4 ± 1.72, p = 0.014). Among IgG subtypes, the IgG1 antibody was significantly higher in hemophilia patients than control group (p < 0.001). The frequency of CD4+ as well as CD8+ T cells did not significantly differ between patients and control group (p > 0.05). There was no significant difference between patients with and without inhibitors re-garding serum immunoglobulin level, different IgG subtypes, the frequency of CD4+ and CD8+ T cells as well as CD4/CD8 ratio (p > 0.05).

CONCLUSIONS

Patients with hemophilia A have high levels of serum immunoglobulin especially IgG1. Therefore, further larger studies along with close observation and evaluation of the presence of serum inhibitor is recommended every 3 months.