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Thromb Haemost 2000; 84(03): 374-380
DOI: 10.1055/s-0037-1614031
Commentary
Schattauer GmbH

Heterogeneous Recognition of beta 2-glycoprotein I by Antibodies from Antiphospholipid Syndrome Patients

J. Guerin
1   From the Department of Immunology, St. James’s Hospital, Dublin
,
R. Sim
2   MRC Immunochemistry Unit, Dept. of Biochemistry, University of Oxford, UK
,
B-B. Yu
2   MRC Immunochemistry Unit, Dept. of Biochemistry, University of Oxford, UK
,
J. Ferluga
2   MRC Immunochemistry Unit, Dept. of Biochemistry, University of Oxford, UK
,
C. Feighery
1   From the Department of Immunology, St. James’s Hospital, Dublin
,
J. Jackson
3   Dublin Institute of Technology, Dublin, Ireland
› Author AffiliationsThe authors would like to thank Mr. Anthony Willis who performed the amino acid sequencing of the digested fragment of β2-GPI at the MRC Immunochemistry Unit, Dept. of Biochemistry, University of Oxford.
Further Information

Publication History

Received 22 December 1999

Accepted after resubmission 04 April 2000

Publication Date:
14 December 2017 (online)

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Summary

Beta 2-glycoprotein I plays a pivotal role in the binding of antiphospholipid antibodies to phospholipid in patients with antiphospholipid syndrome. In this study the nature of the epitopes on beta 2-glycoprotein I (β2-GPI) recognised by sera from antiphospholipid syndrome (APS) patients (n = 15) was investigated and compared to rabbit polyclonal and mouse monoclonal anti-β2-GPI antibodies. β2-GPI was only recognised when bound to a high affinity binding support. The antigenic epitope on β2-GPI recognised by all APS patients was also dependent on disulphide bond integrity. Digestion of β2-GPI with elastase rapidly destroyed the epitope(s) on β2-GPI recognised by antibodies in 91% of APS patients. The main cleavage occurred at tryptophan316-lysine317 in the fifth domain. Digestion with staphylococcal V8 protease resulted in a 50% reduction in antibody binding in 81% of patients and the cleavage sites mainly involved the first domain of the molecule. There was considerable variability in the recognition of six different species of β2-GPI by serum from APS patients. The epitopes on β2-GPI bound by APS sera appear conformationally determined in all patients but are quite heterogeneous in the regions of β2-GPI that are recognised.

Key words

Beta 2-glycoprotein I - antibodies - antiphospholipid syndrome - heterogeneity - species
 

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