Inhibitors and Immune Tolerance Induction in Hemophilia A

A balancing act

Schep, Sarah

prof.dr R.E.G. (Roger) Schutgens & prof.dr J.J. (Jan) Voorberg
Dr M.L. (Marianne) Boes & dr K. (Kathelijn) Fischer
Research group:
December 23, 2021
14:15 h


One of the main complications in the treatment of hemophilia A is the development of antibodies against factor VIII (FVIII), so called inhibitors. This thesis was aimed to explore mechanisms involved in inhibitor development as well as the eradication of inhibitors by means of Immune Tolerance Induction (ITI). In conclusion, inhibitor patients express significantly lower frequency of regulatory B-cells (Bregs) and regulatory markers on CD4+ T-cells, which are restored by successful ITI. Our findings suggest that an existing anti-FVIII immune response is associated with deficits in peripheral tolerance mechanisms and that Bregs and changes in immunoregulatory properties of CD4+ T-cells likely contribute to ITI in hemophilia A patients with inhibitors.

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