Thromb Haemost 2001; 86(04): 1070-1076
DOI: 10.1055/s-0037-1616535
Special Article
Schattauer GmbH

Oxidation of β2-glycoprotein I (β2GPI) by the Hydroxyl Radical Alters Phospholipid Binding and Modulates Recognition by anti- β2GPI Autoantibodies

J. Arvieux
1   Laboratoire d’Immunologie, Institut de Synergie des Sciences et de la Santé, CHU Brest, France
,
V. Regnault
2   Laboratoire d’Hématologie, Faculté de Médecine, Nancy, France
,
E. Hachulla
3   Service de Médecine Interne, CHU Lille, France
,
L. Darnige
4   Département de Biologie Clinique, CH Compiègne, France
,
F. Berthou
5   Laboratoire de Biochimie, EA-948, Faculté de Médecine Brest, France
,
P. Youinou
1   Laboratoire d’Immunologie, Institut de Synergie des Sciences et de la Santé, CHU Brest, France
› Author Affiliations
Further Information

Publication History

Received 15 December 2000

Accepted after resubmission 06 June 2001

Publication Date:
09 December 2017 (online)

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Summary

We investigated whether β2-glycoprotein I (β2GPI), the key antigen in the antiphospholipid syndrome, is susceptible to oxidative modifications by the hydroxyl radical (°OH) that may influence its lipid-binding and antigenic properties. The effects on human and bovine β2GPI of °OH free radicals generated by γ-radiolysis of water with 137Cs were studied. Radiolytic °OH caused a dose-dependent loss of tryptophan, production of dityrosine and carbonyl groups, dimerization and/or extensive aggregation of β2GPI. It ensued a reduction in affinity binding to cardiolipin liposomes and loss of β2GPI-dependent autoanti-body binding to immobilized cardiolipin. Patient anti- β2GPI antibodies (n = 20) segregated into two groups based on the effect in the β2GPIELISA of β2GPI pretreatment with °OH: enhancement (group A, n = 10) or suppression (group B, n = 10) of IgG binding. The avidities of group A antibodies for fluid-phase β2GPI were low but increased in a dose-dependent manner upon β2GPI irradiation, in relation to protein crosslinking. Distinguishing features of group B antibodies included higher avidities for fluid-phase β2GPI that was no longer recognized after °OH treatment, and negative anticardiolipin tests suggesting epitope location near the phospholipid binding site. The °OH scavengers thiourea and mannitol efficiently protected against all above changes. Therefore, oxidative modifications of β2GPI via °OH attack of susceptible amino acids alter phospholipid binding, and modulate recognition by autoantibodies depending on their epitope specificities. These findings may be of clinical relevance for the generation and/or reactivity of anti- β2GPI antibodies.

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