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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
1   La Jolla Pharmaceutical Company, San Diego, CA
,
Jeffrey S. Dlott
2   Midwest Hemostasis and Thrombosis Laboratories, Medical Education Department, Ball Memorial Hospital, Muncie, IN
,
Richard A. Furie
3   Division of Rheumatology and Allergy-Clinical Immunology, North Shore University Hospital-NYU School of Medicine, Manhasset, NY
,
Richard M. Jack
4   Triad Therapeutics, San Diego, CA
,
Thomas L. Ortel   *
5   Department of Medicine, Duke University Medical Center, Durham, NC, USA
,
Douglas A. Triplett
2   Midwest Hemostasis and Thrombosis Laboratories, Medical Education Department, Ball Memorial Hospital, Muncie, IN
,
Edward J. Victoria
1   La Jolla Pharmaceutical Company, San Diego, CA
,
Matthew D. Linnik   *
1   La Jolla Pharmaceutical Company, San Diego, CA
› Author Affiliations
Further Information

Publication History

Received 18 December 2000

Accepted after revision 16 March 2001

Publication Date:
12 December 2017 (online)

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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

* TLO is supported by a Research Grant from the Arthritis Foundation and a Midcareer Investigator Award in Patient-Oriented Research (1 K24 AI01603-01) from the NIH.


 

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