Libman-Sacks endocarditis associated with antiphospholipid syndrome and infection.
BACKGROUND
Antiphospholipid 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-cardiolipin/beta2 glycoprotein I (beta2GPI) antibodies in the valve specimens derived from APS patients. The involvement of complement C3c in the pathogenesis was documented. We assessed the beta2GPI-related target epitope recognized by the anti-beta2GPI Abs on the valves.


METHODS
In order to find the beta2GPI-related target epitopes recognized by the anti-beta2GPI antibodies on the valves, we used beta2GPI-related synthetic peptides. The presence of anti-beta2GPI Abs on the studied valves was detected by anti-idiotypic antibody, followed by immunoperoxidase analysis. Biotin attached to the N-terminal of beta2GPI-related synthetic peptides and control peptide were used to identify the epitope addressed by the anti-beta2GPI 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 beta2GPI-related 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-beta2GPI Abs deposited on the APS valves. This synthetic peptide was able to displace the anti-anti-beta2GPI anti-idiotypic Abs for binding the anti-beta2GPI Abs on the valve by a competition assay.


CONCLUSIONS
We point to the possibility that Libman-Sacks nonbacterial endocarditis may have an infectious origin.
Blank
M
M
Department of Medicine B, The Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel.
Shani
A
A
Goldberg
I
I
Kopolovic
J
J
Amigo
M C
MC
Magrini
L
L
Shoenfeld
Y
Y
D017153:Antibodies, Anticardiolipin / Q000737:chemistry; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology*; D004696:Endocarditis / Q000150:complications / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry; D006023:Glycoproteins / Q000276:immunology; D006351:Heart Valves / Q000378:metabolism; D006801:Humans; D007239:Infections / Q000150:complications; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D000939:Epitopes; D006023:Glycoproteins; D010455:Peptides; D053482:beta 2-Glycoprotein I