Rheumatic Heart Disease and Myxomatous Degeneration: Differences and Similarities of Valve Damage Resulting from Autoimmune Reactions and Matrix Disorganization.

Autoimmune inflammatory reactions leading to rheumatic fever (RF) and rheumatic heart disease (RHD) result from untreated Streptococcus pyogenes throat infections in individuals who exhibit genetic susceptibility. Immune effector mechanisms have been described that lead to heart tissue damage culminating in mitral and aortic valve dysfunctions. In myxomatous valve degeneration (MXD), the mitral valve is also damaged due to non-inflammatory mechanisms. Both diseases are characterized by structural valve disarray and a previous proteomic analysis of them has disclosed a distinct profile of matrix/structural proteins differentially expressed. Given their relevance in organizing valve tissue, we quantitatively evaluated the expression of vimentin, collagen VI, lumican, and vitronectin as well as performed immunohistochemical analysis of their distribution in valve tissue lesions of patients in both diseases. We identified abundant expression of two isoforms of vimentin (45 kDa, 42 kDa) with reduced expression of the full-size protein (54 kDa) in RHD valves. We also found increased vitronectin expression, reduced collagen VI expression and similar lumican expression between RHD and MXD valves. Immunohistochemical analysis indicated disrupted patterns of these proteins in myxomatous degeneration valves and disorganized distribution in rheumatic heart disease valves that correlated with clinical manifestations such as valve regurgitation or stenosis. Confocal microscopy analysis revealed a diverse pattern of distribution of collagen VI and lumican into RHD and MXD valves. Altogether, these results demonstrated distinct patterns of altered valve expression and tissue distribution/organization of structural/matrix proteins that play important pathophysiological roles in both valve diseases.

Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases.

BACKGROUND: Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. METHODS: This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. RESULTS: There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. CONCLUSIONS: There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.

[THE ROLE OF TRANSFORMING GROWTH FACTOR-B IN IMMUNOPATHOGENESIS OF DISEASES OF CONNECTIVE TISSUE].

The recent studies of molecular physiology of fibrillin and pathophysiology of inherent disorders of structure and function of connective tissue such as dissection and aneurysm of aorta, myxomatously altered cusps and prolapses of mitral valve, syndrome of hyper-mobility of joints, demonstrated that important role in development of these malformations play alterations of transfer of signals by growth factors and matrix cellular interaction. These conditions under manifesting Marfan's syndrome can be a consequence of anomalies of fibrillin-1 which deficiency unbrakes process of activation of transforming growth factor-ß (TGFß). The involvement of TGFß in pathogenesis of Marfan's syndrome permits consider antagonists of angiotensin-transforming enzymes as potential pharmaceuticals in therapy of this disease. The article presents analysis of publications' data related to this problem.

[Immune state in athletes with mitral valve prolapse].

The authors evaluated immune state in 541 professional athletes. The athletes with vitral valve prolapse (132 subjects) appeared to have immune changes - lower immunoglobulines levels, general leucocytes count, if compared to the athletes without mitral valve prolapse.

Pathogenic aspects of dermatomyositis, polymyositis and overlap myositis.

Inflammatory myopathies (IMs) often have distinct histopathologic features suggesting humorally mediated involvement of the microcirculation in dermatomyositis (DM), including early capillary deposition of the complement C5b-9 membranolytic attack complex (MAC) and secondary ischaemic changes; and CD8 T-cell-mediated and MHC1-restricted autoimmune attack of myofibers in polymyositis (PM) and inclusion body myositis. Novel insights in these specific diseases include emerging evidence that capillary loss involves whole microvascular units in DM, and that regulatory T-cells strongly protect myofibers from experimental autotoxic attack in PM. However, all IMs do not exhibit pathophysiology-relevant histopathologic features of DM or PM. Autoimmune necrotizing myopathies (AINM) occur in the absence of endomysial inflammatory cells and may be specifically associated with anti-SRP autoantibodies. Moreover, IM histopathological features may be scarce, unspecific and overlapping. Therefore, increasing attention is paid to features shared by IMs regardless of their type, relevant to the innate immune response and to non-immune mechanisms. Innate immune responses to myodamage (and/or as yet unknown stimuli), involves release of chemokines, activation of specific Toll-like receptors (TLRs) and complex Th-1, Th-17 and other cytokine interplays; it triggers DC recruitment and maturation, and is associated with type 1 IFN signature (especially in DM where type 1 IFN-producing cells called plasmacytoid DCs are mainly detected). Non-immune mechanisms mainly include endoplasmic reticulum (ER) stress induced in myofibers by up-regulation of MHC-class I antigens (as typically observed in PM with a diffuse pattern and in DM with perifascicular predominance). ER stress may favour autoimmune reactions but may also be associated with myofiber damage and dysfunction in the absence of lymphocytes. Overlap myositis (OM) may be associated with other connective tissue diseases and a variety of autoantibodies, such as those directed against tRNA synthetase. Myositis specific autoantibodies are mainly expressed by regenerating myofibers, that may also express MHC-1 and endogenous ligand-binding TLRs, thus drawing a picture in which the regenerating myofiber plays a central pathophysiologic role.

Mitral valve prolapse in young healthy individuals. An early index of autoimmunity?

Mitral valve prolapse (MVP) is a benign valvular abnormality. However, an increased prevalence of MVP is reported in patients with systemic lupus erythematosus and autoimmune thyroid disease. Our aim was to evaluate whether the presence of MVP in healthy individuals might indicate a premature index of subclinical autoimmune disorder. A total of 75 individuals with MVP and 44 individuals without MVP were identified by echocardiography. Serum samples were examined for various organ and non-organ specific autoantibodies. In all, 35 of the 75 individuals with MVP had at least one autoantibody. ANA were detected in 17/75 in MVP(+) versus 1/44 in the MVP(-), (P < 0.05), and anti-ENA in 6/75 in the MVP(+) versus 0/44 in the control group, P = ns. In the MVP(+) group, thyroid autoantibodies, IgA and IgG RF were found at a statistically significant higher incidence, 16/75, 11/75 and 10/75 versus 1/44, 0/44 and 0/44 in the MVP(-)group, respectively (P < 0.05). The levels of IgG anticardiolipin antibodies were significantly higher in the MVP(+) group, P < 0.05. The presence of organ and non-organ specific autoantibodies in young healthy MVP(+) individuals insinuate the presence of subclinical autoimmunity and might suggest that autoimmune mechanisms might be involved in its pathogenesis. A follow-up of these individuals might elucidate whether MVP constitutes an early index of autoimmunity.

[Low ability of blood lymphocytes to produce interferon-gamma in patients with idiopathic prolapse of mitral valve].

AIM: To examine lymphocyte ability to synthetize interferon-gamma in patients with mitral prolapse (MP). MATERIAL AND METHODS: The diagnosis of MP was made in 75 patients at echocardiography. ECG monitoring was made and the study of the ability of blood lymphocytes to produce IFN-gamma (If-g). RESULTS: The ability to produce If-g was diminished. This phenomenon is associated with chronic inflammation, autonomic disregulation of cardiac activity, depends on gender. CONCLUSION: Cytokine modulates metabolism of connective tissue in MP so If-g may participate in MP pathogenesis. Therefore, If-g and/or its inductors may prevent some MP-related complications due to its deficiency.

Mitral valve prolapse in systemic lupus erythematosus patients: clinical and immunological aspects.

Mitral valve prolapse (MVP) has been reported to be associated with systemic lupus erythematosus (SLE). The aim of the present study was to determine the prevalence of MVP in SLE patients, assess its clinical significance and examine the possible association of this entity with other autoimmune indices. Eighty-seven consecutive SLE patients attending the rheumatology clinic and 73 normal control subjects were examined by M-mode, two-dimensional color-Doppler echocardiography. Serum samples were examined for various organ and non-organ specific autoantibodies. MVP was detected in 19/87 patients with SLE and in four of the healthy controls(P = 0.0057). SLE patients with MVP were younger (33.6 +/- 12.4 years) than those without MVP (41. +/- 12.9, P = 0.04) and with shorter duration of the disease (P = 0.03). We found a statistically higher prevalence of anticardiolipin antibodies (aCL) in SLE patients with prolapse (11/19) compared with SLE patients without prolapse (15/68, P = 0.04). This association was independent of age. The aCL-lgG levels were significantly higher in SLE patients with MVP (32.37 +/- 43.26) compared with SLE patients without MVP (22.24 +/- 29.95, P = 0.04). Thyroid autoantibodies tended to be more common in S LE patients with MVP. Th e prevalence of MVP is increased in SLE patients. The presence of aCL and of organ-specific autoantibodies in SLE patients with MVP might indicate the autoimmune origin of MVP. The possibility that SLE patients with MVP may be predisposed to further autoimmune diseases should be considered.

Relationship between IFN-gamma production by blood lymphocytes and constitutional personality features of patients with idiopathic mitral valve prolapse.

Psychological testing using Eysenck Personality Inventory and immunological testing of 75 patients with idiopathic mitral valve prolapse revealed low production of interferon-gamma by blood lymphocytes and a correlation between interferon-gamma production and patient's temperament. Low neuroticism and extroversion scores were found in patients with normal interferon-gamma production. High neuroticism score was detected in 82% patients with lowest interferon-gamma production, which refers these patients to a group at high immunological risk and prompts the use of interferon and/or its inductors in complex therapy of these patients.

Reiter's syndrome caused by Streptococcus viridans in a patient with HLA-B27 antigen.

A 26-year-old male patient with mitral valve prolapse and HLA-B27 antigen received endodontic treatment for dental caries. Two weeks later fever, dysuria, diarrhea, sterile inflammatory arthritis of lower limbs, enthesitis, dactylitis, conjunctivitis, and uveitis consecutively developed. Blood culture performed at the time of active arthritis yielded Streptococcus viridans. He did not have any history of psoriasis, acute infectious diarrhea, chronic inflammatory bowel diseases, or sexually transmitted diseases. Laboratory studies also excluded the possibility of infections by human immunodeficiency virus, hepatitis B or C virus, chlamydia, and streptococci from the upper airway. This report indicates that Streptococcus viridans can be the triggering microorganisms of Reiter's syndrome in some circumstances.

Cardiac involvement in Behçet's disease.

To assess the prevalence and the extent of cardiac involvement in patients with Behçet's disease and to investigate the possible causes that may predispose to this involvement, 30 patients affected by Behçet's disease and 30 normal control subjects were submitted to M-mode, two-dimensional, and Doppler echocardiographic evaluation. Moreover, antinuclear and anticardiolipin autoantibodies were determined in the sera of both patients and control subjects. Finally, HLA-B51 positivity was assessed in the patients and in a historical control group. Mitral valve prolapse was observed in 50% and proximal aorta dilatation in 30% of the patients. There was a significant difference in the rate of these abnormalities in comparison with the control group. Left ventricular function parameters were similar between the two groups. The positivity rate of antinuclear and anticardiolipin autoantibodies was very low (7%), without differences between the groups. HLA-B51 was detected in 82.7% of the patients versus 21.7% in the control group (p < 0.00001). In conclusion, this study demonstrates a high rate of cardiac abnormalities in patients with Behçet's disease.

Frequency of HLA antigens in Graves' hyperthyroidism and mitral valve prolapse.

BACKGROUND AND AIMS OF THE STUDY: An association between Graves' hyperthyroidism (G) and mitral valve prolapse (MVP) has been reported, but possible genetic linkage between the two disorders has not. METHODS: One hundred and five patients (pts) with G were studied after therapy, in a euthyroid state. MVP (auscultatory plus echocardiographic findings) was present in 33 pts (31%). Frequency of human lymphocyte antigens (HLA) in pts with G and in pts with G plus MVP was compared to 170 normal subjects (NL). There was no difference in HLA-A antigens among the three groups. RESULTS: The frequency of HLA B-15 was greater in pts with G plus MVP (18.9%) compared to NL (3%) and to G without MVP (4.2), p < 0.01. The frequency of HLA-B39 was greater in G without MVP (13.8%) compared to NL (4.1%), p < 0.01. The HLA DRB1*1601-2 was more frequent in G with (30.3%) or without (29.2%) MVP compared to NL (13.5%), p < 0.01. The frequency of HLA DRB1*1401-10 and DQA1*0104 were greater in NL (16.5%) compared to G with (3.0%) or without (4.2%) MVP, p < 0.01. CONCLUSIONS: The data confirmed previous observations that the frequency of MVP is high in pts with G. Further, the data indicated a possible genetic linkage between the two abnormalities.

Prevalence of myxomatous mitral valve prolapse in patients with lymphocytic thyroiditis.

In conclusion, given the cardiac (mitral regurgitation, endocarditis, thromboembolic complications, arrhythmic sudden death) and neurologic (cerebral embolic event) complications of the pathologic forms of MVP, physicians should look carefully for myxomatous involvement of the mitral valve and prolapse in patients with autoimmune thyroid diseases. Patients should be monitored and prophylactic antibiotic treatment recommended when appropriate.

Juvenile autoimmune thyroiditis and mitral valve prolapse.

An increased incidence of mitral valve prolapse (MVP) has been reported in adult patients with autoimmune thyroid disease. The aim of this study was to assess the incidence of MVP in children and adolescents with juvenile autoimmune thyroiditis (JAT). Cardiac echo studies using M-mode, 2D, and Doppler examinations were performed on 23 patients (21 females, 2 males). The patients were studied at a median age of 12 years (range 5-20 years). Only one patient was found to have evidence suggestive of MVP, an incidence (4.3%) similar to that seen in the normal pediatric population. We, therefore, conclude that the incidence of MVP in children and adolescence with JAT is not increased.

[HLA antigens and primary prolapse of the mitral valve]. / HLA antigény a primárny prolaps mitrálnej chlopne.

The authors present results of investigation of antigens of the HLA system in primary mitral valvular prolapse. The investigated group of patients was formed by 23 not related patients with primary mitral valvular prolapse. (15 women, 8 men, aged 18-55 years) where HLA antigens of loci A, B and C were assessed. They found a significantly increased frequency of antigen HLA-B35 in the patients (56.52%), as compared with the population (18.33%, x2 = 18.48, Pcorr less than 0.01). The measure of the observed relationship is expressed by the relative risk value--RR = 5.81. The difference in the frequency of the other HLA antigens was not statistically significant.

[Bacterial endocarditis caused by Enterobacter agglomerans in a patient with mitral valve prolapse]. / Bakteryjne zapalenie wsierdzia wywolane przez enterobacter agglomerans u chorego z wypadaniem platka zastawki dwudzielnej.

A case of bacterial endocarditis caused by Enterobacter agglomerans was observed in a 50-year-old patient with mitral valve leaflet prolapse. The diagnosis was based on clinical findings, positive blood cultures and echocardiographic investigations.