Epitope Studies with Anti- beta -glycoprotein I Antibodies from Autoantibody and Immunized Sources

• Published in: Journal of autoimmunity 2000-09, Vol.15 (2), p.91-96
• Main Authors: Reddel, S W, Wang, Y X, Sheng, Y H, Krilis, SA
• Format: Article
• Language: English
• Subjects: antiphospholipid syndrome; b2-glycoprotein I
• ISSN: 0896-8411
• DOI: 10.1006/jaut.2000.0427

This paper examines the methodology of anti- beta sub(2)-glycoprotein I ( beta sub(2)-GPI) epitope determination and provides further epitope studies using human sera containing anti- beta sub(2)-GPI autoantibodies. Studies in this field may be misleading as the antigen coating density using mutant forms of beta sub(2)-GPI may be below the threshold required for monogamous divalent binding by low affinity anti- beta sub(2)-GPI autoantibodies, while being easily detected by high affinity anti- beta sub(2)-GPI from immunized animals. The antigen density threshold effect is found in anti- beta sub(2)-GPI autoantibodies from humans and from monoclonal anti- beta sub(2)-GPI derived from mice with models of autoimmune disease. Anti- beta sub(2)-GPI from an autoimmune mouse and from 18/21 human sera did not bind above background levels to a domain-I-deleted mutant. In addition, single point mutations in domain I result in dramatic changes in the binding of many human sera containing anti- beta sub(2)-GPI. These findings support a conclusion that domain I of beta sub(2)-GPI contains significant epitopes for the anti- beta sub(2)-GPI antibodies found in the antiphospholipid syndrome.