抗カルジオリピン抗体(<特集>膠原病とアフェレシス)

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It has been widely believed that antiphospholipid antibodies(aPL), a family of autoantibodies found in the sera of patients with systemic lupus erythematosus(SLE)and related connective tissue diseases, are immunoglobulins that react with anionic phospholipids(PLs) directly. Further, the appearance of aPL is known to be associated with thromboembolic manifestations. Against this background, recent studies have indicated that such antibodies recognize various phospholipid-binding plasma proteins, such asβ_2-glycoprotein I(β_2-GPI),proth- rombin and annexin V but do not recognize phospholipids directly. It was also reported that anti- az-GPI antibodies, which recognize a cryptic epitope on the Qz-GPI molecule, are dominantly found in so-called anticardiolipin antibodies(aCL)-positive sera, and that the epitope for anti-/3Z-GPI antibodies is expressed by a conformational change occurring when as-GPI interacts with a lipid membrane composed of negatively charged PLs. We recently investigated the interaction between oxidized plasma lipoproteins,β_2-GPI and anti-β_2-GPI antibodies.β_2-GPI specifically bound to oxidized lipoproteins(i.e., oxVLDL, oxLDL or oxHDL)and anti-β_2-GPI antibodies sequentially bound to the az-GPI complexed with oxidized lipoproteins. The binding of oxLDL by macrophage cells was inhibited by the addition of/3z-GPI. Interestingly, the binding was significantly increased by the simultaneous addition of az-GPI and anti-a2-GPI. These findings strongly suggest that oxidized lipoproteins are sequentially targeted byβ_2-GPI and anti-β_2-GPI antibodies, and that this immunoreaction is involved not only in the metabolism of oxidized plasma lipoproteins but also in atherosclerotic events in APS.
日本アフェレシス学会の論文
1997-05-31

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