Nonclassical anti-C2 domain antibodies are present in patients with factor VIII inhibitors.
The antihuman factor VIII (fVIII) C2 domain immune response in hemophilia A mice consists of antibodies that can be divided into 5 groups of structural epitopes and 2 groups of functional epitopes. Groups A, AB, and B consist of classical C2 antibodies that inhibit the binding of fVIII to phospholipid and von Willebrand factor. Groups BC and C contain nonclassical C2 antibodies that block the activation of fVIII by thrombin or factor Xa. Group BC antibodies are the most common and display high specific inhibitory activity and type II kinetics. The C2 epitope groups recognized by 26 polyclonal human anti-fVIII inhibitor plasmas were identified by a novel competition enzyme-linked immunosorbent assay using group-specific murine monoclonal antibodies. Most of the anti-C2 inhibitor plasmas inhibited the binding of both classical and nonclassical antibodies. These results suggest that nonclassical anti-C2 antibodies contribute significantly to the pathogenicity of fVIII inhibitors.
Meeks
Shannon L
SL
Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta, Emory University, Atlanta, GA30322 , USA.
Healey
John F
JF
Parker
Ernest T
ET
Barrow
Rachel T
RT
Lollar
Pete
P
D000818:Animals; D001666:Binding Sites, Antibody; D004797:Enzyme-Linked Immunosorbent Assay; D005169:Factor VIII / Q000276:immunology*; D015951:Factor Xa; D006467:Hemophilia A / Q000276:immunology*; D006801:Humans; D051379:Mice; D013917:Thrombin
D005169:Factor VIII; D013917:Thrombin; D015951:Factor Xa