Autoimmunity in Chagas Disease

Teixeira, Antônio R. L.; Ripoll, Carlos; Santos‐Buch, Charles A.

doi:10.1007/978-1-4613-0347-3_11

Cited by 6 publications

(6 citation statements)

References 55 publications

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“…The bulk of evidence supports the participation of T cells rather than antibody in heart damage (2,3,5,10,35). The association of cardiac myosin HC-B13 crossreactive antibodies with CCC may be only signaling the presence of "helper" T cells of similar specificity, these ones potentially involved in heart tissue damage.…”

Section: Resultsmentioning

confidence: 98%

“…sensitivity responses toward a tissue-specific heart component bearing structural similarities to a given T. cruzi antigen. Several investigators found autoantibody and self-reactive T-cell formation in human and experimental T cruzi infection (5,6). Crossreactive autoantibodies were mainly directed toward ubiquitous and evolutionarily conserved molecules (7,8).…”

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confidence: 99%

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Autoimmunity in Chagas disease cardiopathy: biological relevance of a cardiac myosin-specific epitope crossreactive to an immunodominant Trypanosoma cruzi antigen.

Cunha-Neto¹,

Duranti²,

Gruber³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

190

153

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Heart tissue destruction in chronic Chagas disease cardiopathy (CCC) may be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate decades after Trypanosoma cruzi infection. Indirect evidence suggests that there is antigenic crossreactivity between T. cruzi and heart tissue. As there is evidence for immune recognition of cardiac myosin in CCC, we searched for a putative myosin-crossreactive T. cruzi antigen. T. cruzi lysate immunoblots were probed with anti-cardiac myosin heavy chain IgG antibodies (AMA) affinity-purified from CCC or asymptomatic Chagas disease patient-seropositive sera. A 140/116-kDa doublet was predominantly recognized by AMA from CCC sera. Further, recombinant T. cruzi protein B13--whose native protein is also a 140- and 116-kDa double band--was identified by crossreactive AMA. Among 28 sera tested in a dot-blot assay, AMA from 100% of CCC sera but only 14% of the asymptomatic Chagas disease sera recognized B13 protein (P = 2.3 x 10(-6)). Sequence homology to B13 protein was found at positions 8-13 and 1442-1447 of human cardiac myosin heavy chain. Competitive ELISA assays that used the correspondent myosin synthetic peptides to inhibit serum antibody binding to B13 protein identified the heart-specific AAALDK (1442-1447) sequence of human cardiac myosin heavy chain and the homologous AAAGDK B13 sequence as the respective crossreactive epitopes. The recognition of a heart-specific T. cruzi crossreactive epitope, in strong association with the presence of chronic heart lesions, suggests the involvement of crossreactivity between cardiac myosin and B13 in the pathogenesis of CCC.

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Section: Resultsmentioning

confidence: 98%

mentioning

confidence: 99%

Autoimmunity in Chagas disease cardiopathy: biological relevance of a cardiac myosin-specific epitope crossreactive to an immunodominant Trypanosoma cruzi antigen.

Cunha-Neto¹,

Duranti²,

Gruber³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

190

153

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“…From a clinical point of view, the discrepancies among these theories can be justified, possibly, by the difficulty in determining pathogenicity after a long average time lapse between the acquisition of the T. cruzi infection and the development of severe lesions mainly in the heart, peripheral nervous system, and digestive tube in chronic Chagas' disease (318,398,399,404,407). Specific features in the course of natural T. cruzi infections and of Chagas' disease parallel some postvirus syndromes (210,305).…”

Section: Theories About the Pathogenesis Of Chagas' Diseasementioning

confidence: 99%

“…Now, unadulterated copies of the Cell article can be obtained from Google-cited independent websites.) Various theories have been proposed, beginning with the mechanical action of the parasite encysted in host cells, followed by the subsequent degradation of the affected tissue by inflammation, which was challenged by the neurogenic theory, stemming from a hypothetical parasite-released neurotoxin, and displaced by the current autoimmune theory, in which host tissues are self-rejected by immune system effector lymphocytes (173,293 [see comments regarding this retracted article at first citation], 344,398,402,408).…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

et al. 2011

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SUMMARY Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8 + γδ, and CD8α + T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease.

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“…Cells harboring a high-density parasite load burst open and release differentiated forms that initiate new cycles of infection. Host defense mechanisms can control the reinfection process in moderate or low-density phagocyte invasion (reviewed in Teixeira et al 1996).…”

Section: The Infectious Agent and The Host Organismmentioning

confidence: 99%