Dominant C2 domain epitope specificity of inhibitor antibodies elicited by a heat pasteurized product, factor VIII CPS-P, in previously treated hemophilia A patients without inhibitors

• Published in: Thrombosis and haemostasis Vol. 79; no. 1; p. 62
• Main Authors: Sawamoto, Y, Prescott, R, Zhong, D, Saenko, E L, Mauser-Bunschoten, E, Peerlinck, K, van den Berg, M, Scandella, D
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1998
• Subjects: Adolescent; Adult; Antigen-Antibody Reactions; Child; Child, Preschool; Epitopes; Factor VIII - immunology; Factor VIII - therapeutic use; Hemophilia A - drug therapy; Hemophilia A - immunology; Hot Temperature; Humans; Immunodominant Epitopes; Middle Aged; Protein Structure, Tertiary; Sterilization
• DOI: 10.1055/s-0037-1614221
• ISSN: 0340-6245

From June, 1990, to November, 1991, in The Netherlands and Belgium, 16 previously treated severe hemophilia A patients (PTP) developed inhibitors after exposure to factor VIII CPS-P, a new heat pasteurized product. A previously untreated patient (PUP) also developed an inhibitor to CPS-P. In inhibitor neutralization assays with recombinant fVIII C2 and A2 domain polypeptides, plasmas from 14 PTPs were > or = 79% neutralized by C2 and < 10% by A2, but the PUP plasma was partially neutralized by C2 (48%) and A2 (28%). Immunoprecipitation assays of the PTP and PUP plasmas with the fVIII heavy chain and with recombinant C2 and A3-C1 polypeptides confirmed that the C2 dominant immune response to CPS-P was found only in the PTPs. Competition of the binding of 2 inhibitors to 125I-CPS-P by unlabeled CPS-P and another plasma fVIII was similar, demonstrating that the antibody response was not directed to epitopes only present in CPS-P. We propose that the immunogenicity of the CPS-P C2 domain was altered by heat pasteurization.