The presence of antiautonomic membrane receptor antibodies do not correlate with brain lesions in Chagas' disease

Abstract

-We previously demonstrated correlation between parasympathetic dysfunction and brain white matter lesions in chronic chagasic patients. Objective: To correlate serum functional circulating antibodies with beta adrenergic (Ab-β), muscarinic (Ab-M) or muscarinic and beta adrenergic (Ab-Mβ) activity, the autonomic system function and brain lesions in chronic chagasic patients. Method: In fifteen consecutive chagasic patients, the autonomic nervous system was evaluated and brain magnetic resonance imaging (MRI) was performed. The sera of all patients were tested to the presence of circulating functional antibodies. Results: Sera from 11 of 15 chronic chagasic patients had some activity (Ab-β: 7; Ab-M: 1; Ab-Mβ: 3); however, there was no significant correlation between the presence of antibodies and the autonomic system function or the presence of hyperintensities in MRI. Conclusion: The mechanism involved in the genesis of hyperintense lesions seen in brain MRI of chronic chagasic patients is still unresolved, although apparently related to parasympathetic dysfunction.Key WoRdS: Chagas' disease, American trypanosomiasis, autonomic dysfunction, antibodies, magnetic resonance imaging, hyperintense lesions. a presença de anticorpos anti-autonômicos não se correlaciona a lesões cerebrais na doença de chagas resumo -A correlação entre disfunção parassimpática e lesões de substância branca cerebral em pacientes chagásicos já foi previamente demonstrada. Objetivo: Correlacionar a presença de anticorpos circulantes funcionais com atividade beta-adrenérgica (Ab-β), muscarínica (Ab-M) ou muscarínica e beta adrenérgica (Ab-Mβ), a presença de disautonomia e lesões de substância branca cerebral em pacientes chagásicos crônicos. Método: em quinze pacientes chagásicos consecutivos, foram realizados a avaliação do sistema nervoso autônomo e ressonância magnética (RM) do crânio. o soro dos pacientes foi testado para a presença de anticorpos funcionais circulantes. Resultados: o soro de 11 dos 15 pacientes chagásicos apresentou alguma atividade (Ab-β: 7; Ab-M: 1; Ab-Mβ: 3); porém não houve correlação significativa entre a presença de anticorpos circulantes e disautonomia ou de hiperintensidades à RM. Conclusão: o mecanismo envolvido na gênese das lesões hiperintensas à RM do crânio dos pacientes chagásicos crônicos não está esclarecida ainda, apesar de aparentemente relacionada à disfunção parassimpática.PAlAvRAS-ChAve: doença de Chagas, tripanossomíase americana, disfunção autonômica, anticorpos, ressonância magnética, lesões hiperintensas.

Neurologic Manifestations of Chagas Disease

“…In our series, we found no cognitive disorders in chagasic patients, even in those presenting subcortical white matter lesions [21•]. Also, none of our patients with serum functional circulating antibodies with muscarinic activity presented cognitive dysfunction [23]. In our series, we applied the Mini-Mental Status Examination, a clock drawing test, verbal fluency, the trail making test, the Rey auditory verbal learning test, figural memory, visual memory span, digit span, and mazes [21•].…”

“…The antireceptor antibodies were tested in rabbit isolated hearts. We concluded that the mechanism of the pathobiology involved in the genesis of hyperintense lesions seen on brain MRIs of chronic chagasic patients is still unresolved, although apparently related to parasympathetic dysfunction [23].…”

Pathogenesis and Pathology of Chagas' Chronic Myocarditis

“…These antibodies also caused accumulation of inositol phosphate and nitric oxide synthase stimulation, with a negative inotropic effect on myocardium (Sterin-Borda Leonor, et al, 1997). As mentioned before, anti-muscarinic autoantibodies are positively related to the presence of dysautonomia (Goin J. C., et al, 1994), the presence of achalasia in chagasic patients (Goin J. C., et al, 1999), sinus node dysfunction (Altschuller, et al, 2007), but are not related with the degree of myocardial dysfunction (Altschuller, et al, 2007, Talvani Andre, et al, 2006, nor with the presence of brain lesions (Py, et al, 2009). In fact, patients with cardiomyopathy and left ventricular dysfunction but without autonomic dysfunction show low levels of anti-muscarinic antibodies (Sterin-Borda Leonor & Borda, 2000).…”

Pathogenesis of Chronic Chagasic Myocarditis

“…These antibodies also causes accumulation of inositol phosphate and nitric oxide synthase stimulation, with a negative inotropic effect on myocardium [71]. As mentioned before, anti-muscarinic autoantibodies are positively related to the presence of dysautonomia [70], the presence of achalasia in chagasic patients [72], sinus node dysfunction [73], but are not related with the degree of myocardial dysfunction [73,74], nor with the presence of brain lesions [75]. In fact patients with cardiomyopathy and left ventricular dysfunction but without autonomic dysfunction show low levels of anti-muscarinic antibodies [76].…”