title: Highly conserved antigenic structure of the factor VIII C2 domain in some mammals.
abstract: To elucidate differences in the antigenic structure of factor VIII (FVIII) among mammals, we evaluated cross-reactivities of well-defined antihuman FVIII antibodies with canine and other mammalian FVIII proteins. Monoclonal antibodies against human FVIII recognizing the A1 domain in the heavy chain and the A3 domain in the light chain showed 2.7% and 0% cross-reactivities, respectively, with canine FVIII. The cross-reactivities of 2 alloantibodies and a monoclonal antibody that recognized the A2 domain in the heavy chain were 10%, 38%, and 0%, respectively. On the other hand, 2 kinds of alloantibodies and a monoclonal antibody recognizing the C2 domain in the light chain showed 160%, 390%, and 130% cross-reactivity, respectively, with canine FVIII. The anti-C2 monoclonal antibody (NMC-VIII/5) showed a type 2 inactivating property when tested with canine and human plasma. Moreover, cross-reactivities of NMC-VIII/5 with simian and feline FVIII were 54.5% and 82.8%, respectively, while the cross-reactivities of the anti-A2 monoclonal antibody (JR8) with simian and feline FVIII were 1.3% and 0%, respectively. These findings suggest that the antigenic structure of the C2 epitope has remained relatively conserved throughout mammalian evolution in contrast to the A2 epitope and that a canine model of hemophilia A is useful for FVIII inhibitor experiments.
authors.affiliation: Ori Animal Hospital, Osaka, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Ori
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tanaka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kubota
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshioka
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000737:chemistry; D001777:Blood Coagulation; D017124:Conserved Sequence; D003429:Cross Reactions; D004285:Dogs; D005169:Factor VIII / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007518:Isoantibodies; D008322:Mammals; D046912:Multiprotein Complexes
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D007518:Isoantibodies; D046912:Multiprotein Complexes; D005169:Factor VIII