Are Oxidized LDLβ2-glycoprotein I Complexes Pathogenic Antigens in Autoimmune-mediated Atherosclerosis英文文献资料.docVIP

ClinicalDevelopmentalImmunology,June2004,Vol.11(2),pp.103–111 AreOxidizedLDL/b2-glycoproteinIComplexesPathogenic AntigensinAutoimmune-mediatedAtherosclerosis? EIJIMATSUURAa,*andLUISR.LOPEZb aDepartmentofCellChemistry,OkayamaUniversityGraduateSchoolofMedicineandDentistry,2-5-1Shikata-cho,Okayama700-8558,Japan; bCorgenix,Inc.,Westminster,CO80234,USA Theoxidativemodi?cationoflow-densitylipoprotein(LDL)intheintimaofarteriescontributestothe initiationandprogressionofatheroscleroticlesions.WehavepreviouslyreportedthatoxidizedLDL (oxLDL)interactswithanendogenousplasmaprotein,b2-glycoproteinI(b2GPI),toformcomplexes andthattheinteractionismediatedbyoxLDLspeci?cligands.Wehavealsodemonstratedthepresence of oxLDL/b2GPI complexes in the blood stream of patients with systemic in?ammatory and autoimmunediseases.These?ndingsimplicatethatoxLDL/b2GPIcomplexesarepossibleatherogenic autoantigens. Autoantibodies to oxLDL/b2GPI complexes have been associated with arterial thrombosis. Further, circulating IgG immune complexes containing oxLDL and b2GPI were also detected in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Although many unanswered questions remain about the exact pathogenic mechanism(s) involved,oxLDL/b2GPIcomplexesmaybedescribedasmetabolicproductsrelevantinatherogenesis andassigni?cantparticipantsinautoimmune-mediatedatherosclerosis. Keywords: Antiphospholipidsyndrome;Antiphospholipidantibody;OxidizedLDL;b2-glycoproteinI; Atherosclerosis INTRODUCTION anticardiolipin (aCL), lupus anticoagulants (LA) and/or other antiphospholipid antibodies. It is now commonly accepted that the plasma protein b2-glycoprotein I (b2GPI)representsamajorantigenictargetforantiphos- pholipid antibodies in patients with APS (McNeil et al., 1990; Galli et al., 1990; Matsuura et al. , 1990, 1992,1994). Atherosclerosis is a major health concern of worldwide importance.Theexperimentalevidencehasestablisheda causal relationship between atherosclerosis and l