Autoantibodies in Chagas' Cardiomyopathy and Arrhythmias

Anti-muscarinic autoantibodies and vagal modulation in Chagas disease: Positive allosteric modulators vs desensitization and downregulation of M2 cardiac acetylcholine receptors

“…Nonetheless, the RR intervals, in time and frequency domain analysis at rest and during tilt, of elderly chagasic are not different from those age-matched nonchagasic individuals [17]. Therefore, the opposite findings of these clinical investigations should be taken into consideration when analyzing Ribeiro's [7] results and conclusions [18,19]. Further research is urgently needed to clarify this very important and controversial issue [20,21].…”

Crystal Structure of the Complex mAb 17.2 and the C-Terminal Region of Trypanosoma cruzi P2β Protein: Implications in Cross-Reactivity

“…Furthermore, as severe cases of chronic Chagas' Heart Disease are related to high levels of Abs directed against the R13 epitope [8], [17], [18], [19], [20], [23], [49], and immuno-purified anti-R13 Abs from some of these patients showed in common that R13 residues Glu3, Asp6 and Phe9 were essential for recognition [23] (as was shown for mAb 17.2), we suggest that high blood concentrations of these antibodies may exert a systemic effect by inducing functional changes in cell types and tissues expressing this receptor, thereby increasing liability to chronic pathology from T. cruzi infection.…”

“…The cardiac form, referred as chronic Chagas' heart disease (cChHD), is not only the most frequent and severe consequence of the chronic infection by T. cruzi , but is also the main cause of cardiomyopathy in South and Central America [6]. Among other clinical features, cChHD is an arrhythmogenic cardiomyopathy with high prevalence of right bundle branch block, left anterior hemi block, sinus node dysfunction and complex supraventricular arrhythmias [7], [8]; mega disorders of colon or esophagus and neurological disorders are less frequent (around 5% of the infected people) [9], [10]. To date, the mechanisms of the pathophysiology of Chagas' disease are not completely understood and two main hypotheses have been proposed: the first is based on the essential role of the parasite in tissular damage while the second argues for an auto reactive process resulting from an impaired immune response associated with molecular mimicry [11], [12], [13].…”

Effects on heart rate of an anti‐M2 acetylcholine receptor immune response in mice

“…The pathogenic properties of anti-␤ 1 adrenoceptor autoantibodies have been ascribed to their potency to continuously stimulate the sympathetic drive, since the autoantibodies inhibit receptor desensitization (30). In contrast to Chagas' cardiomyopathy, in which sinus node dysfunction and bradycardia can be correlated with a dominant anti-M2ACh-R response (31), dilated cardiomyopathy has a dominant anti-␤1 adrenoceptor response, although an anti-M2ACh-R response was found in 43% of patients (17). The presence of anti-M2 AChR autoantibodies in DCM could be an example of immunological homeostasis in which the activity of anti-M2ACh-R antibodies, as described here, could compensate for the continuous sympathetic drive induced by the anti-␤1 adrenoceptor autoantibodies.…”