title: Antiphospholipid reactivity against cardiolipin metabolites occurring during endothelial cell apoptosis.
abstract: We have recently shown that cardiolipin (CL) and its metabolites move from mitochondria to other cellular membranes during death receptor-mediated apoptosis. In this study, we investigate the immunoreactivity to CL derivatives occurring during endothelial apoptosis in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We compared the serum immunoreactivity to CL with that of its derivatives monolysocardiolipin (MCL), dilysocardiolipin (DCL), and hydrocardiolipin (HCL) by means of both enzyme-linked immunosorbent assay and thin-layer chromatography (TLC) immunostaining. In addition, we investigated the composition of phospholipid extracts from the plasma membrane of apoptotic endothelial cells and the binding of patients' sera to the surface of the same cells by using high-performance TLC and immunofluorescence analysis. The average reactivity to MCL was comparable with that of CL and significantly higher than that for DCL and HCL in patients studied, both in the presence or in the absence of beta2-glycoprotein I. Of relevance for the pathogenic role of these autoantibodies, immunoglobulin G from patients' sera showed an increased focal reactivity with the plasma membrane of endothelial cells undergoing apoptosis. Interestingly, the phospholipid analysis of these light membrane fractions showed an accumulation of both CL and MCL. Our results demonstrated that a critical number of acyl chains in CL derivatives is important for the binding of antiphospholipid antibodies and that MCL is an antigenic target with immunoreactivity comparable with CL in APS and SLE. Our finding also suggests a link between apoptotic perturbation of CL metabolism and the production of these antibodies.
authors.affiliation: Dipartimento di Clinica e Terepia Medica, Cattedra e Divisione di Reumatologia, Università La Sapienza, viale del Policlinico 155, Roma, 00161, Italy. cristianoalessandri@hotmail.com
authors.forename: Cristiano
authors.initials: C
authors.lastname: Alessandri
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sorice
authors.forename: Michele
authors.initials: M
authors.lastname: Bombardieri
authors.forename: Paola
authors.initials: P
authors.lastname: Conigliaro
authors.forename: Agostina
authors.initials: A
authors.lastname: Longo
authors.forename: Tina
authors.initials: T
authors.lastname: Garofalo
authors.forename: Valeria
authors.initials: V
authors.lastname: Manganelli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Conti
authors.forename: Mauro Degli
authors.initials: MD
authors.lastname: Esposti
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
mesh_terms: D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000276:immunology* / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D002308:Cardiolipins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D002855:Chromatography, Thin Layer; D042783:Endothelial Cells / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D017152:Antibodies, Antiphospholipid; D002308:Cardiolipins; D007074:Immunoglobulin G