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Evaluation of antiphospholipid antibodies (aPL) and correlation with heart valve abnormalities among patients with systemic lupus erythematosus (SLE). Nested case-control study was conducted with 70 patients with SLE selected from a longitudinal database based on levels of aPL and presence or absence of valve disease by echocardiogram. Valvular abnormalities observed were regurgitation (52), other (14), artificial valves (4), stenosis (2), thickening (2) and no Libman-Sacks endocarditis (0). The mitral valve was the most commonly affected (30 abnormalities), followed by the tricuspid (20 abnormalities). Multivariate logistic regression for those with and without an aPL value ≥20 units/mL, adjusted for disease duration and age, showed significant differences for any valve abnormality (odds ratio [OR] = 3.1; 95% CI: 1.0-8.9; P = 0.041) and individually for the tricuspid valve (OR = 3.3; 95% CI: 1.0-11.1; P = 0.052) but not for the mitral valve (OR = 2.1; 95% CI: 0.68-6.45; P = 0.195). Levels of aPL ≥20 units/mL showed no association with aortic (P = 0.253), pulmonic (P = 1.000), tricuspid (P = 0.127), or mitral (P = 0.249) valve abnormalities. Levels of aPL correlate with certain valvular abnormalities among patients with SLE., (Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

We currently use a rat model in our investigations into human rheumatic heart disease (RHD). This model traditionally involves footpad immunization with antigen emulsified in complete Freund's adjuvant (CFA). Trials to find an alternative adjuvant to CFA which produced a Th1 type response in the rats resulting in carditis were unsuccessful. However, hock immunization was found to produce the desired valvular pathology without the adverse inflammatory side-effects associated with CFA. We therefore consider the hock an ideal site for immunization, particularly when using CFA., (Copyright 2010 Elsevier B.V. All rights reserved.)

Immune responses against cardiac myosin and group A streptococcal M protein have been implicated in the pathogenesis of rheumatic heart disease. Although cardiac myosin is known to produce myocarditis in susceptible animals, it has never been investigated for its role in production of valvular heart disease, the most serious sequelae of group A streptococcal infection in acute rheumatic fever. In our study, cardiac myosin induced valvulitis in the Lewis rat, and epitopes responsible for production of valvulitis were located in the rod region. Human and rat cardiac myosins induced severe myocarditis in the Lewis rats as expected. A purified S2 fragment (amino acid sequences 842 to 1295) produced the most severe myocarditis as well as valvulitis. Different regions of light meromyosin produced valvulitis (residues 1685 to 1936) or myocarditis (residues 1529 to 1611). Because streptococcal M proteins produced valvular heart disease in Lewis rats and have been linked to anti-cardiac myosin responses, we reacted myosin-sensitized lymphocytes isolated from the hearts of Lewis rats with peptides of streptococcal M5 protein in tritiated thymidine assays. Infiltrating lymphocytes responded most strongly to peptides within the B repeat region of streptococcal M protein. These data show direct evidence that immune responses against cardiac myosin lead to valvular heart disease and the infiltration of the heart by streptococcal M protein reactive T lymphocytes.

The aim of this study was to determine the prevalence of cardiac valve disease in systemic lupus erythematosus or in patients with primary antiphospholipid syndrome and to assess the role of the antiphospholipid antibodies as risk factor for endocardial lesions. We studied 39 consecutive patients with systemic lupus erythematosus (mean age 34 +/- 12 years, 38 female and one male), 20 women with primary antiphospholipid syndrome (mean age 32 +/- 4 years) and 20 normal subjects (mean age 35 +/- 8 years, 15 female and five male). All patients with primary antiphospholipid syndrome had increased levels of serum anticardiolipin antibodies and recurrent fetal abortions; some of them also had arterial and/or venous thrombosis and/or thrombocytopenia. M-mode, two-dimensional and Doppler echocardiography were performed in all patients. IgG anticardiolipin antibodies were measured by an enzyme-linked immunosorbent assay. Valvular lesions were observed in 15 patients (38%) with systemic lupus erythematosus. These abnormalities included: mitral valve thickening or vegetation, mitral valve prolapse and aortic valve vegetation; mitral, aortic and tricuspid regurgitation; mitral stenosis. None of the patients with primary antiphospholipid syndrome and of the normal subjects was found to have valvular abnormalities. In systemic lupus erythematosus, high levels of anticardiolipin antibodies were detected in 73% of the patients with valvular lesions and in 67% of the patients without valvular lesions (P > 0.05). We conclude that valvular involvement is frequent in patients with systemic lupus erythematosus but it is apparently unrelated to antiphospholipid autoimmunization.

Association of group A streptococci with acute rheumatic fever and valvular heart disease is well established; however the basis of valve injury remains unclear. In this study, anti-streptococcal monoclonal antibodies (MAbs) cross-reactive with myocardium were reacted with sections from 22 rheumatic valves, nine normal, five endocarditic, one 'floppy,' and one Marfan valve. In immunohistochemical studies, MAb reactivity was observed with cardiac myocytes, smooth muscle cells, cell surface and cytoplasm of endothelial cells lining valves, and valvular interstitial cells. Endothelial basement membrane and elastin fibrils reacted with the MAbs, whereas collagen was unreactive. Similar reactivity was seen with sera from acute rheumatic fever patients. The anti-streptococcal MAbs reacted with intravalvular myosin and vimentin in Western blots, and purified elastin competitively inhibited the binding of the anti-streptococcal MAbs to whole group A streptococci. The data show that human heart valves have numerous sites of immunoreactivity with anti-streptococcal MAbs and acute rheumatic fever sera of potential importance in the pathogenesis of rheumatic valvular injury.

A prospective echocardiographic study was carried out on 132 consecutive patients with systemic lupus erythematosus (SLE) derived from three European university medical centres. The prevalence of valvular lesions in patients with SLE was 22.7% compared with 2.9% in a control group of 68 healthy volunteers. 50 SLE patients had antibodies against phospholipids. The prevalence of valve vegetations (8/50 [16%]) and of mitral regurgitation (19/50 [38%]) was significantly higher among the SLE patients with antiphospholipids than among those without (1 and 10/82 [1.2% and 12%], respectively). During follow-up of the patients with valvular lesions, haemodynamically significant clinical valve disease developed in 6 but surgery was required in only 1; 9 had cerebrovascular occlusions; and 7 died, although no death was due directly to the cardiac involvement. Thus, valvular heart disease, particularly affecting the mitral valve, is common in patients with SLE, and the presence of antibodies against phospholipids is associated with a higher prevalence of valvular abnormalities in these patients.