The hololipoprotein complex of beta(2)-glycoprotein I and dicaproyl phosphatidylserine.
The ability of beta(2)-glycoprotein I (formerly referred to as apolipoprotein H) to act as an autoantigen for antibodies from patients with antiphospholipid syndrome is dependent upon its binding in vivo to anionic phospholipid surfaces or to surfaces in vitro which mimic their surface characteristics. The ability of the autoepitope(s) of beta(2)-glycoprotein I to be exposed by binding a short-chain (6-carbon), anionic phospholipid has not been explored. Here, we describe our studies of the hololipoprotein generated by reacting beta(2)-glycoprotein I with dicaproyl phosphatidylserine. The formation of the complex is accompanied by inhibition of beta(2)-glycoprotein I binding to phospholipid-coated polystyrene surfaces, with 50% reduction in binding occurring at about 10 mM. At concentrations >10 mM, dicaproyl phosphatidylserine also displaces beta(2)-glycoprotein I bound to anionic phospholipid surfaces. Physicochemical studies suggest that at DCPS concentrations >6 mM, the solutions are colloidal and that beta(2)-glycoprotein I forms a supramolecular complex with organized phospholipid structures. Using a standard human autoimmune anti-beta(2)-glycoprotein I plasma, as well as a series of six additional sera from patients with antiphospholipid syndrome, the complex did not generate a detectable epitope. We conclude that lipid binding, per se, is not sufficient for the presentation of the epitope(s) of beta(2)-glycoprotein I or its recognition by autoantibodies from patients with antiphospholipid syndrome.
Kohles
J D
JD
The Laboratory of Experimental Medicine, Department of Medicine, St. Joseph's Hospital and Medical Center, 703 Main Street, Paterson, NJ, 07503, USA.
Petersheim
M
M
DeBari
V A
VA
D016736:Antiphospholipid Syndrome / Q000276:immunology; D001323:Autoantibodies; D001324:Autoantigens / Q000737:chemistry / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D010718:Phosphatidylserines / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D012996:Solutions; D053482:beta 2-Glycoprotein I
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D006023:Glycoproteins; D046911:Macromolecular Substances; D010718:Phosphatidylserines; D012996:Solutions; D053482:beta 2-Glycoprotein I