Autoimmunity in Chagas' disease

Schmuñis, Gabriel A.

doi:10.1590/s0074-02761987000500011

Cited by 32 publications

(15 citation statements)

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“…It is characterized by focal or disseminated inflammatory infiltrates, myocytolysis, and myonecrosis and progressive deposition of fibrotic tissue (11,29). The intensity of the myocarditis varies considerably from light cardiac symptoms to intense chronic cardiomyopathy, leading to heart failure and death (31). Patients with chronic chagasic cardiomyopathy may have diverse arrhythmias that cause heart malfunction.…”

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confidence: 99%

Treatment with Benznidazole during the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations

Garcia

Ramos

Senra

et al. 2005

Antimicrob Agents Chemother

225

160

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Chagas' disease, caused by Trypanosoma cruzi infection, is one of the main causes of death due to heart failure in Latin American countries. Benznidazole, the chemotherapeutic agent most often used for the treatment of chagasic patients, is highly toxic and has limited efficacy, especially in the chronic phase of the disease. In the present study we used a mouse model of chronic Chagas' disease to investigate the effects of benznidazole treatment during the chronic phase on disease progression. The hearts of benznidazole-treated mice had decreased parasitism and myocarditis compared to the hearts of untreated chagasic mice. Both groups of Trypanosoma cruzi-infected mice had significant alterations in their electrocardiograms compared to those of the healthy mice. However, untreated mice had significantly higher cardiac conduction disturbances than benznidazole-treated mice, including intraventricular conduction disturbances, atrioventricular blocks, and extrasystoles. The levels of antibodies against T. cruzi antigens (epimastigote extract, P 2 ␤, and transsialidase) as well as antibodies against peptides of the second extracellular loops of ␤ 1 -adrenergic and M 2 -muscarinic cardiac receptors were also lower in the sera from benznidazole-treated mice than in the sera from untreated mice. These results demonstrate that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication. In addition, our data highlight the role of parasite persistence in the development of chronic Chagas' disease and reinforce the importance of T. cruzi elimination in order to decrease or prevent the development of severe chagasic cardiomyopathy.

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confidence: 99%

Treatment with Benznidazole during the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations

Garcia

Ramos

Senra

et al. 2005

Antimicrob Agents Chemother

225

160

View full text Add to dashboard Cite

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“…A chronic phase follows spontaneously about 2 months later, when the parasitemia declines significantly and becomes subclinical. The complex pathology at chronicity also varies considerably, ranging from light cardiac symptoms to intense chronic cardiomyopathy leading to heart failure and death (32). In some areas, patients may also develop clinical pathology in the digestive tract of variable intensity with or without heart involvement (1).…”

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confidence: 99%

“…The mechanisms responsible for the cardiomyopathy are not clearly understood, but the occurrence of chronic myocardial injury in the near absence of parasites suggests an autoimmune phenomenon (32). Nevertheless, the hypothesis of an autoimmune disorder in Chagas' disease remains controversial (16).…”

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confidence: 99%

Modulation of Cardiocyte Functional Activity by Antibodies againstTrypanosoma cruziRibosomal P2 Protein C Terminus

et al. 2000

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Antibodies against the Trypanosoma cruzi ribosomal P2␤ protein (TcP2␤) have been associated with the chronic cardiac pathology of Chagas' disease in humans. Using synthetic peptides spanning the entire TcP2␤ molecule, we investigated their epitope recognition by antibodies from mice chronically infected with T. cruzi and from mice immunized with two recombinant TcP2␤s. We found clear differences in epitope recognition between antibodies from T. cruzi-infected mice and mice immunized with two different recombinant TcP2␤s associated with different schedules of immunization. Major epitopes recognized by antibodies from mice immunized with recombinant glutathione S-transferase (GST) or histidine (Hist) fusion TcP2␤ (GST-TcP2␤ or HistTcP2␤) are located in the central and hinge regions of the molecule. Nevertheless, mice immunized with Hist-TcP2␤ were also able to elicit antibodies against the TcP2␤ C terminus, a region which is highly conserved in both T. cruzi and mammal ribosomal P proteins. Strikingly, antibodies from infected animals recognized only the TcP2␤ C terminus. By using these antisera with distinct profiles of epitope recognition, it could be shown that only C terminus-specific antibodies were able to increase the beating frequency of cardiomyocytes from neonatal rats in vitro by selective stimulation of the ␤1-adrenergic receptor. Thus, antibodies against the TcP2␤ C terminus elicited in the absence of infection are able to modulate a functional activity of host cells through a molecular mimicry mechanism.

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“…Recent data indicate that the development of chronic lesions, which seem to be mediated in a large extent by autoimmune mechanisms (Teixeira et al 1975, Schmuñis 1987, Cunha-Neto et al 1995, seems to depend on the persistence of parasite infection (Jones et al 1993, Higuchi et al 1993, Brandariz et al 1996, Vago et al 1996, Levin 1996. Therefore the need to find appropriate new drugs, or new protocols with existing drugs, that can be used in the treatment of Chagas disease in order to prevent the development of serious clinical forms (De Andrade et al 1996, Urbina et al 1996, Luquetti 1997.…”

Section: The Unfinished Research and Development (Randd) Agendamentioning

confidence: 99%

Chagas disease, from discovery to control - and beyond: history, myths and lessons to take home

Morel

1999

Mem. Inst. Oswaldo Cruz

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Autoimmunity in Chagas' disease

Cited by 32 publications

References 0 publications

Treatment with Benznidazole during the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations

Treatment with Benznidazole during the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations

Modulation of Cardiocyte Functional Activity by Antibodies againstTrypanosoma cruziRibosomal P2 Protein C Terminus

Chagas disease, from discovery to control - and beyond: history, myths and lessons to take home

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