Libman-Sacks endocarditis associated with antiphospholipid syndrome and infection

Introduction: Anti phospholipid syndrome (APS) is a systemic autoimmune disease, associated not only with a hypercoagulable state and recurrent fetal loss but with many diverse clinical manifestations including heart involvement, neurological manifestations, as well as skin, kidney and hematologic abnormalities. Cardiac manifestations include coronary by-pass graft and angioplasty occlusions, cardiomyopathy, cyanotic congenital heart disease, intracardiac thrombus and complications of cardiovascular surgery. The valvular heart disease was defined as Libman-Sacks nonbacterial endocarditis. Previously, we have shown a linear subendothelial deposition of anti-cardiotipin/beta(2) glycoprotein I (beta 2GPI) antibodies in the valve specimens derived from APS patients. The involvement of complement C3c in the pathogenesis was documented. We assessed the beta 2GPI-related target epitope recognized by the anti-beta 2GPI Abs on the valves. Materials and methods: In order to find the beta 2GPI-retated target epitopes recognized by the anti-beta 2GPI antibodies on the valves, we used beta 2GPI-related synthetic peptides. The presence of anti-beta 2GPI Abs on the studied valves was detected by anti-idiotypic antibody, followed by immunoperoxidase analysis. Biotin attached to the N-terminal of beta 2GPI-related synthetic peptides and control peptide were used to identify the epitope addressed by the anti-beta 2GPI Abs deposited on the patient's valve. The binding was probed by streptavidin-peroxidase and appropriate substrate. The specificity was confirmed by competition assays with control peptide and anti-idiotypic antibody. Results: Among the beta 2GPI-retated synthetic peptides, two peptides were found in previous studies to mimic common pathogens either bacteriae or viruses, which raised a possible infectious origin for APS. One of these peptides, TLRVYK, is a specific target for anti-beta 2GPI Abs deposited on the APS valves. This synthetic peptide was able to displace the anti-anti-beta 2GPI anti-idiotypic Abs for binding the anti-beta 2GPI Abs on the valve by a competition assay. Conclusion: We point to the possibility that Libman-Sacks nonbacterial endocarditis may have an infectious origin. (c) 2004 Elsevier Ltd. All rights reserved.