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Dilated cardiomyopathy (DCM), characterised by a severe dysfunction of the heart muscle, often results from a myocarditis, which could be caused by a variety of organisms or mediated by autoimmune responses to the exposure of cardiac specific antigen, such as myosin, after cardiomyocyte damage. DCM of humans can be experimentally reproduced in susceptible mouse strains by immunisation with purified cardiac myosin.1 Moreover, chlamydia infection may mediate heart disease through an antigenic mimicry between the chlamydia outer membrane protein and muscle specific α myosin of the heart.2 The aim of this study was to investigate the prevalence of Chlamydia pneumoniae infection by measuring the serum IgG and IgA antibodies against C pneumoniae in patients with DCM.
Twenty six consecutive patients with DCM, aged 56.9 (15.5) years, diagnosed according to the World Health Organization/International Society and Federation of Cardiology criteria,3 were enrolled. Twenty eight healthy subjects, mean (SD) age 57.4 (13.7) years, matched for age and sex, were used as the controls; they were chosen from the subjects undergoing coronary angiography during the same period and not showing any significant coronary stenosis, valvar disease or other cardiovascular diseases. None of the patients had a clinical history of specific heart muscle disease that may have caused left ventricular dysfunction nor any systemic and endocrine diseases. All patients were classified into New York Heart Association (NYHA) functional class I–IV based on the presence or absence of dyspnoea during their daily activities. Routine ECGs, chest radiographs, two dimensional echocardiograms, and coronary angiography were performed on all the patients.
Serum concentrations of anti-C pneumoniae specific IgG and IgA antibodies were measured using a new enzyme linked immunosorbent assay (ELISA) method that usesC pneumoniae specific outer membrane protein as the antigen (Hitachi Chemical Co, Tokyo, Japan). Recent investigations have shown that the ELISA methods is more sensitive and specific than immunofluorescence used previously for detecting the antibodies to C pneumoniae, and it may be the preferred tool for diagnosing chlamydia infections in routine clinical practice.4 Briefly, specimens, diluted 210-fold for IgG and 21-fold for IgA, were added to microtitre plates packaged by specific antigen and the optical density was measured at 405 nm after incubation. The correction coefficient and the cut-off point were determined by the mean absorption of the positive and negative controls, then the cut-off values of the samples were calculated using the formula of “sample's absorption” (correction coefficient/cut-off point). The seropositivity of both IgG and IgA antibodies was defined as the following criteria: cut-off value < 1.10 for negative (−), ⩾ 1.10 positive (+), respectively. Data were expressed as the mean (SD) or percentage deviation and the analysis was performed using the Statistical Analysis System (SAS). Differences between the two groups were assessed with the unpaired Student's t test for continuous variables and χ2 test for categorical variables. Significance was established at the p < 0.05 level.
The patients with DCM were characterised by the clinical manifestations of left ventricular dysfunction or congestive heart failure, such as tachycardia (88.5 (31.0) v 70.1 (10.8) beats/min, p < 0.05), increased cardiothoracic ratio (58.6 (7.5)v 49.9 (5.6), p < 0.001), and higher NYHA score (2.3 (0.7) v 1.3 (0.5), p < 0.001). Moreover, the serum concentrations of acute phase proteins, which reflect the degree of inflammation, such as C-reactive protein (1.8 (3.5) v 0.1 (0.2) mg/dl, p < 0.05) and fibrinogen (382.2 (112.5) v 278.4 (51.6) mg/dl, p < 0.001), were significantly higher in DCM subjects compared with controls. The echocardiographic data also suggested left ventricular functional impairment in patients with DCM, such as left ventricular diastolic dimension (64.8 (10.1) mmv 46.5 (4.4) mm, p < 0.001) and left ventricular systolic dimension (55.2 (10.0) mmv 29.3 (5.2) mm, p < 0.001). As shown in fig 1, after adjusting for age and sex, the mean value of IgA antibody against C pneumoniae in the controls were significantly different from the DCM patients (0.9 (0.6)v 1.6 (1.0), p < 0.01). However, no significant difference in IgG value was observed between the two groups (1.0 (0.6) v 1.4 (0.9)). The prevalence of IgA antibody was detected in 17/26 (65.4%) of DCM patients and in 8/28 (28.6%) of the controls (p < 0.01), but no significant difference was observed for IgG prevalence between the two groups (14/26 (53.8%)v 10/28 (35.7%)).
DCM could be mediated by autoimmune responses to the cardiac α myosin heavy chain, by which inflammatory heart disease in humans can be experimentally reproduced in susceptible mouse strains.5 A recent study has proved that a peptide from the murine cardiac α myosin heavy chains that has sequence homology to the 60 kD cysteine-rich outer membrane protein of chlamydia was shown to induce autoimmune inflammatory heart disease in mice, suggesting chlamydia mediated heart disease is induced by antigenic mimicry of a heart muscle specific protein.2 On the other hand,C pneumoniae, previously known as TWAR-strain, is an obligate intracellular parasite and tends to cause persistent infection. Several cases of myocarditis caused byC pneumoniae infection have been reported and TWAR was recently identified by polymerase chain reaction in the myocarditis heart.
Our study showed that there was a higher value and more frequent seropositivity of IgA antibody against C pneumoniae in patients with DCM, indicating that the prevalence of persistent infection with C pneumoniaewas higher in patients with DCM because an increased IgA antibody often reflects an active or persistent infection, but the level IgG antibody reflects only a previous or past infection with C pneumoniae infection.5 Although the role ofC pneumoniae infection in the pathogenesis of DCM was not fully elucidated in this study, it could be speculated that C pneumoniae infection associates with DCM by at least three mechanisms as follows: causing chronic and persistent inflammation of the heart muscle; damaging the infected cardiomyocytes and exposing myocardial myosin to the immune system; and inducing an autoimmune response by its antigenic mimicry with a cardiac myosin peptide.
Our study provides the first clinical evidence that DCM in humans could be associated with persistent C pneumoniaeinfection. Since the infection is treatable, an attempt at early diagnosis and effective antibiotic treatment againstC pneumoniae might be considered in patients with cardiomyopathy.
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