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

Yoshikatsu Sawamoto; Richard Prescott; Degang Zhong; Evgueni L. Saenko; Eveline Mauser-Bunschoten; Kathelijne Peerlinck; Marijke van den Berg; Dorothea Scandella

doi:10.1055/s-0037-1614221

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 79(01): 62-68
DOI: 10.1055/s-0037-1614221

Review Article

Schattauer GmbH

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

Authors

Yoshikatsu Sawamoto

¹From the American Red Cross, Rockville, MD, USA
Richard Prescott

¹From the American Red Cross, Rockville, MD, USA
Degang Zhong

¹From the American Red Cross, Rockville, MD, USA
Evgueni L. Saenko

¹From the American Red Cross, Rockville, MD, USA
Eveline Mauser-Bunschoten

²van Creveld Kliniek, Utrecht, The Netherlands
Kathelijne Peerlinck

³Katholieke Universiteit Leuven, Belgium
Marijke van den Berg

²van Creveld Kliniek, Utrecht, The Netherlands
Dorothea Scandella

¹From the American Red Cross, Rockville, MD, USA

Abstract

Summary

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 ≥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.

Full Text

References

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