Price B E, Rauch J, Shia M A, Walsh M T, Lieberthal W, Gilligan H M, O'Laughlin T, Koh J S, Levine J S
Evans Memorial Department of Clinical Research, Boston University Medical Center Hospital, MA 02118, USA.
J Immunol. 1996 Sep 1;157(5):2201-8.
Anti-phospholipid autoantibodies (aPL) are associated with a clinical syndrome of hypercoagulability, thrombocytopenia, and fetal loss. Several groups have shown that the in vitro target of many aPL is not a pure phospholipid Ag, but is either a complex between anionic phospholipid and the plasma protein beta2-glycoprotein I (beta 2GPI) or the protein beta 2GPI alone. Anionic phospholipids are normally absent from the extracellular surface of cell membranes but redistribute from the inner to the outer leaflet during apoptosis. We show that aPL bind specifically to apoptotic, but not viable, thymocytes, and that binding is dependent upon the presence of beta 2GPI. Moreover, we show that beta 2GPI binds selectively to the surface of apoptotic thymocytes to generate an epitope for antiphospholipid autoantibodies. These findings suggest that apoptotic cells may be the natural immunogen and/or target for aPL. Moreover, we propose that the interaction of circulating beta 2GPI with redistributed anionic phospholipid may itself generate a novel ligand by which apoptotic cells are recognized directly for phagocytic clearance.
抗磷脂自身抗体（aPL）与高凝状态、血小板减少和胎儿丢失的临床综合征相关。多个研究小组已表明，许多aPL在体外的靶标并非单纯的磷脂抗原，而是阴离子磷脂与血浆蛋白β2-糖蛋白I（β2GPI）之间的复合物，或者仅是蛋白β2GPI。阴离子磷脂通常不存在于细胞膜的细胞外表面，但在细胞凋亡过程中会从内膜重新分布到外膜。我们发现，aPL特异性结合凋亡的胸腺细胞，而非存活的胸腺细胞，且这种结合依赖于β2GPI的存在。此外，我们还表明β2GPI选择性地结合凋亡胸腺细胞的表面，以产生抗磷脂自身抗体的表位。这些发现表明，凋亡细胞可能是aPL的天然免疫原和/或靶标。此外，我们提出循环中的β2GPI与重新分布的阴离子磷脂之间的相互作用本身可能产生一种新的配体，通过该配体凋亡细胞可被直接识别以便进行吞噬清除。
