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 autoantibody binding to immobilized cardiolipin. Patient anti-β2GPI antibodies (n = 20) segregated into two groups based on the effect in the β2GPI-ELISA 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.
CITATION STYLE
Arvieux, J., Regnault, V., Hachulla, E., Darnige, L., Berthou, F., & Youinou, P. (2001). Oxidation of beta2-glycoprotein I (beta2GPI) by the hydroxyl radical alters phospholipid binding and modulates recognition by anti-beta2GPI autoantibodies. Arthritis Research & Therapy, 3(S2). https://doi.org/10.1186/ar251
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