title: To clear or to fear: An innate perspective on factor VIII immunity.
abstract: The enigma that is factor VIII immunogenicity remains ever pertinent in the treatment of hemophilia A. Development of neutralizing antibodies against the therapeutic protein in 25-30% of patients likely depends on the appropriate activation of the innate immune response shortly following antigen encounter. Our understanding of this important immunological synapse remains ill-defined. In this review, we examine the three distinct factors contributing to the fate of factor VIII almost immediately after infusion: the characteristics of the protein, the cell, and the microenvironment. We propose a continuum between clearance and antigen presentation that facilitates removal of FVIII from circulation leading to either tolerance or immunity.
authors.affiliation: Department of Pathology & Molecular Medicine, Queen's University, Kingston, Canada.
authors.forename: Jesse Derek
authors.initials: JD
authors.lastname: Lai
authors.affiliation: Department of Pathology & Molecular Medicine, Queen's University, Kingston, Canada.
authors.forename: Maria Teofana
authors.initials: MT
authors.lastname: Georgescu
authors.affiliation: Department of Pathology & Molecular Medicine, Queen's University, Kingston, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Hough
authors.affiliation: Department of Pathology & Molecular Medicine, Queen's University, Kingston, Canada. Electronic address: david.lillicrap@queensu.ca.
authors.forename: David
authors.initials: D
authors.lastname: Lillicrap
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D005169:Factor VIII / Q000276:immunology*; D006467:Hemophilia A / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D005169:Factor VIII
keywords: Antigen presenting cells; Clearance; Factor VIII; Hemophilia A; Immune tolerance; Inhibitors; Innate immunity