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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1540-1545.
Prepublished online as a Blood First Edition Paper on October 26, 2004; DOI 10.1182/blood-2004-09-3387.
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Submitted September 1, 2004
Accepted October 19, 2004
IgG antibodies that recognize epitope Gly40-Arg43 in domain I of  2-glycoprotein I cause LAC and their presence correlates strongly with thrombosis
Bas de Laat, Ronald H Derksen, Rolf T Urbanus, and Philip G de Groot*
Department of Haematology, University Medical Centre, Utrecht, The Netherlands
Department of Rheumatology and Clinical Immunology, University Medical Centre, Utrecht, The Netherlands
* Corresponding author; email: ph.g.degroot{at}lab.azu.nl.
Anti- 2-glycoprotein I antibodies are known to have a heterogeneous reactivity against 2-glycoprotein I. We performed this study to characterize the epitope on 2-glycoprotein I to which pathological anti-2-glycoprotein I antibodies are directed. Plasma samples from 198 patients with various systemic autoimmune diseases were tested for the presence of lupus anticoagulant and anti-2-glycoprotein I IgG antibodies. The reactivity of the anti-2-glycoprotein I positive samples was further tested by coating recombinant full-length 2-glycoprotein I and eight deletion mutants of 2-glycoprotein I onto hydrophilic and hydrophobic ELISA plates. Full-length 2-glycoprotein I with point mutations in domain I at positions 8 , 40 and 43 were used in inhibition experiments. Fifty-two patients with anti-2-glycoprotein I IgG antibodies could be divided into two patterns. Type A antibodies only recognize domain I when coated onto hydrophobic plates, they do not recognize domain I coated onto hydrophilic plates. Type B antibodies have heterogeneous reactivity for all domains. Type A antibodies recognize the epitope around amino acids Gly40-Arg43 and cause lupus anticoagulant activity. In contrast to type B antibodies, those of type A strongly correlated with thrombosis. In conclusion, antibodies directed at domain I (epitope comprising Gly40 and Arg43) have lupus anticoagulant activity and strongly associate with thrombosis.
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