Requirements for immune recognition and processing of factor VIII by antigen-presenting cells

Simon D. Van Haren, Aleksandra Wroblewska, Kathelijn Fischer, Jan Voorberg, Eszter Herczenik

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Generation of inhibitory antibodies upon repeated FVIII infusion represents a major complication in hemophilia care. Professional antigen presenting cells (APCs) are crucial for orchestration of humoral immune responses. APCs are capable of internalizing soluble as well as particulate antigens through various mechanisms resulting in loading of antigen-derived peptides on MHC class I or II for presentation to T cells. This review highlights how FVIII is recognized and processed by APCs. The significance and contribution of candidate receptors involved in FVIII uptake by APC are discussed. Recent findings defining the repertoire of FVIII peptides presented on MHC class II are addressed. Studies in murine models of hemophilia A suggest that modulation of APC function can reduce inhibitor formation. Based on this we anticipate that modulation of FVIII uptake by APCs may yield novel therapeutic approaches for treatment or prevention of inhibitor formation in patients with hemophilia A.

Original languageEnglish
Pages (from-to)43-49
Number of pages7
JournalBlood Reviews
Volume26
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • Antigen-presenting cell
  • Factor VIII
  • Hemophilia A
  • Immune response
  • Inhibitors

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