β2-glycoprotein I-dependent Anticardiolipin Antibodies Preferentially Bind the Amino Terminal Domain of β2-glycoprotein I

Patricia A. McNeeley; Jeffrey S. Dlott; Richard A. Furie; Richard M. Jack; Thomas L. Ortel; Douglas A. Triplett; Edward J. Victoria; Matthew D. Linnik

doi:10.1055/s-0037-1616091

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 86(02): 590-595
DOI: 10.1055/s-0037-1616091

Review Article

Schattauer GmbH

β₂-glycoprotein I-dependent Anticardiolipin Antibodies Preferentially Bind the Amino Terminal Domain of β₂-glycoprotein I

Patricia A. McNeeley

¹La Jolla Pharmaceutical Company, San Diego, CA

,

Jeffrey S. Dlott

²Midwest Hemostasis and Thrombosis Laboratories, Medical Education Department, Ball Memorial Hospital, Muncie, IN

,

Richard A. Furie

³Division of Rheumatology and Allergy-Clinical Immunology, North Shore University Hospital-NYU School of Medicine, Manhasset, NY

,

Richard M. Jack

⁴Triad Therapeutics, San Diego, CA

,

Thomas L. Ortel^*

⁵Department of Medicine, Duke University Medical Center, Durham, NC, USA

,

Douglas A. Triplett

²Midwest Hemostasis and Thrombosis Laboratories, Medical Education Department, Ball Memorial Hospital, Muncie, IN

,

Edward J. Victoria

¹La Jolla Pharmaceutical Company, San Diego, CA

,

Matthew D. Linnik^*

¹La Jolla Pharmaceutical Company, San Diego, CA

› Author Affiliations

Abstract

Summary

Many of the autoantibodies in antiphospholipid syndrome (APS) are directed against β₂-glycoprotein I (β₂-GPI). Recent studies from our laboratories have indicated that the immunodominant binding epitope(s) for high titer, affinity purified antibodies from 11 APS patients are localized to the amino terminal domain (domain 1) of β₂-GPI. The present study employed surface plasmon resonance to localize the immunodominant domain in serum samples from a large cohort of patients with GPL values ranging from 21 to 230 units (n = 106 patients). Eighty-eight percent of patients showed ≥ threefold selectivity for β₂-GPI containing domain 1 relative to the domain deletion mutant that lacked domain 1. The domain 1 binding activity in patient serum was abolished by removing the IgG fraction from the serum and the binding activity could be fully reconstituted with the IgG fraction. Thus, analysis of serum samples from a large cohort of APS patients indicates that the immunodominant binding epitope(s) for anti- ₂ antibodies are localized to the amino terminal domain of β₂-GPI.

Keywords

Anticardiolipin antibodies - antiphospholipid syndrome - β₂-glyco-protein I

Full Text

References

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