Mariarosaria Miranda: I Successfully Defended my PhD!
Mariarosaria Miranda, PhD in Immunohematology at Sanquine, shared on LinkedIn:
”I am excited to share that on 06/11/25, I successfully defended my PhD!
My thesis, “A stranger no more: re-educating the immune system to FVIII in hemophilia A,” explored the development of inhibitory antibodies against factor VIII (FVIII), a major challenge in hemophilia A treatment, and how we can modulate the immune system toward tolerance.
In brief, my work investigated several complementary strategies to better understand and modulate the immune response to FVIII:
• Mapping FVIII peptide presentation on HLA-DP molecules (especially HLA-DP4) to identify immunodominant peptides that could inform future tolerance-inducing therapies.
• Using red blood cells (RBCs) as delivery platforms for FVIII–TAT fusion peptides, showing efficient uptake by immune cells and highlighting RBCs as a promising carrier system.
• Engineering FVIII–Annexin A5 fusion proteins, exploiting apoptotic clearance pathways to promote tolerogenic antigen presentation.
• Studying FVIII-containing immune complexes, pointing to the inhibitory receptor FcγRIIb as a potential target to dampen dendritic cell activation.
• Characterizing anti-FVIII antibodies in a large patient cohort to clarify the role of non-neutralizing antibodies as markers of inhibitor risk or immune modulation.
Together, these findings contribute to a deeper understanding of FVIII immunogenicity and open multiple avenues for developing targeted immune tolerance strategies in hemophilia A.
My heartfelt thanks to my promoters, Jan Voorberg and Karin Fijnvandraat, and to my supervisor Maartje van den Biggelaar, for their guidance, encouragement, and trust throughout this journey.
A special thank you to the EDUC8 consortium and to the MSCA for supporting my research and providing an inspiring international training environment.
I’m grateful for everyone who has been part of this chapter, colleagues, collaborators, friends, and family.
Exciting news ahead, stay tuned!”
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