PXD069058-1

PXD069058 is an original dataset announced via ProteomeXchange.

Title	Exploring red blood cells as an antigen delivery system to modulate the immune response towards FVIII in hemophilia A
Description	Background: The main complication in hemophilia A treatment is the development of inhibitory antibodies against factor (F)VIII. Immune tolerance induction, the gold standard for eradicating anti-FVIII antibodies, is efficient in only 60% to 80% of cases. This underscores the need for more efficient induction of tolerance in patients with hemophilia A with FVIII inhibitors. Objectives: In this study, we explored whether red blood cells (RBCs) can be utilized as antigen delivery system to modulate the immune response against FVIII. Methods: Two promiscuously HLA-DR–presented peptides derived from the A2 and C1 domains of FVIII were fused to the TAT cell-penetrating peptide and incubated with RBCs. Results: Biotinylated TAT-A2 and TAT-C1 peptides were found to interact with RBCs as shown by flow cytometry and imaging flow cytometry. Moreover, macrophages efficiently phagocytosed TAT-FVIII peptide–treated RBCs. Using mass spectrometry– based immunopeptidomics we established that TAT-FVIII peptides were presented on major histocompatibility complex class II of macrophages that phagocytosed TAT peptide–pulsed RBCs. Specifically, the TAT-A2 peptide exhibited efficient processing and presentation on HLA-DR molecules. Importantly, incubation of TAT-C1 peptide– treated RBCs-loaded macrophages with a FVIII-specific T-cell hybridoma led to a significant increase in IL-2 production, suggesting functional presentation of TAT-C1– derived peptides by macrophages. Conclusion: Our findings indicate that RBCs can serve as effective vehicle for the delivery of FVIII-derived peptides to antigen-presenting cells. The successful display of T-cell epitopes on antigen-presenting cell using ex vivo–loaded RBC may be potentially utilized to modulate pathogenic immune responses such as observed in a subset of patients with hemophilia A.
HostingRepository	PRIDE
AnnounceDate	2025-10-02
AnnouncementXML	Submission_2025-10-02_02:29:26.124.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Arie Hoogendijk
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-01 16:36:52	ID requested
⏵ 1	2025-10-02 02:29:27	announced

10.1016/j.jtha.2024.11.012;

Miranda M, Brandsma E, Robben L, Van Dender H, van Alphen FPJ, Fijnvandraat K, van den Biggelaar M, Lacroix-Desmazes S, van Bruggen R, Voorberg J, Exploring red blood cells as an antigen delivery system to modulate the immune response towards FVIII in hemophilia A. J Thromb Haemost, 23(3):836-848(2025) [pubmed]

submitter keyword: hemophilia A,erythrocytes, inhibitors, immunity, factor VIII

A.J. Hoogendijk
contact affiliation	Sanquin Research, Amsterdam, NL
contact email	a.hoogendijk@sanquin.nl
lab head
Arie Hoogendijk
contact affiliation	Sanquin Research, Amsterdam
contact email	a.hoogendijk@sanquin.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069058
     1. Label: PRIDE project
     2. Name: Exploring red blood cells as an antigen delivery system to modulate the immune response towards FVIII in hemophilia A