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Chapter 18 : Molecular Mimicry and Chagas' Disease

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Abstract:

Chronic Chagas' disease cardiomyopathy (CCC) is one of the few well-defined examples of human postinfectious autoimmunity in which an infectious episode with an established pathogen—the protozoan parasite —clearly triggers autoimmune phenomena, most of which are related to documented molecular mimicry and organ-specific damage. Unraveling of the relationship by which molecular mimicry between an infectious agent and self-components can trigger organ-specific autoimmunity may lead to reverse strategies for the identification of infectious agents that putatively trigger autoimmune diseases of suspected infectious etiology. Chagas' disease is a conundrum of several clinical syndromes triggered by infection in a group of susceptible individuals. An array of reports of autoreactivity among Chagas' disease patients and experimentally infected animals has been published over the last three decades. Experimental models of dilated cardiomyopathy have been developed with larger outbred animals, like rabbits and dogs. The chapter critically reviews reports on such models, with an emphasis on those that report on molecular mimicry between and host target organs. Taken together, these reports on cardiac myosin autoimmunity in murine models of Chagas' disease suggested the possible relevance of myosin recognition in the pathogenesis of CCC in humans. The study of fine recognition and immune repertoires in diseases in which molecular mimicry is thought to play a role is probably going to become an important focus of research in the near future.

Citation: Cunha-Neto E, Kalil J. 2000. Molecular Mimicry and Chagas' Disease, p 257-274. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch18

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Figure 1

Prevalence of immunoglobulin G antibodies cross-reactive with cardiac myosin and B13 protein in sera from CCC patients and ASY individuals (percent positive) (modified from reference ).

Citation: Cunha-Neto E, Kalil J. 2000. Molecular Mimicry and Chagas' Disease, p 257-274. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch18
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Image of Figure 2
Figure 2

Cross-reactive recognition of cardiac myosin and protein B13 by T-cell clones E205 (black bars) and E2.17 (white bars) derived from heart tissue from a CCC patient (modified from reference ).

Citation: Cunha-Neto E, Kalil J. 2000. Molecular Mimicry and Chagas' Disease, p 257-274. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch18
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Image of Figure 3
Figure 3

Cross-reactive recognition of cardiac myosin (black bars) and protein B13 (white bars) by T-cell clones obtained from a PBMC T-cell line sensitized with B13 protein. The synthetic peptide p313 (hatched bars) is a negative control (modified from reference ).

Citation: Cunha-Neto E, Kalil J. 2000. Molecular Mimicry and Chagas' Disease, p 257-274. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch18
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Tables

Generic image for table
Table 1

Autoreactivity after infection

Citation: Cunha-Neto E, Kalil J. 2000. Molecular Mimicry and Chagas' Disease, p 257-274. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch18
Generic image for table
Table 2

Passive transfer of lesions or functional damage with antibodies or T cells from chronically -infected individuals

Citation: Cunha-Neto E, Kalil J. 2000. Molecular Mimicry and Chagas' Disease, p 257-274. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch18
Generic image for table
Table 3

Molecular mimicry after infection: human disease

Citation: Cunha-Neto E, Kalil J. 2000. Molecular Mimicry and Chagas' Disease, p 257-274. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch18
Generic image for table
Table 4

Molecular mimicry after infection: murine models

Citation: Cunha-Neto E, Kalil J. 2000. Molecular Mimicry and Chagas' Disease, p 257-274. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch18
Generic image for table
Table 5

Induction of heart disorders after immunization with antigens

Citation: Cunha-Neto E, Kalil J. 2000. Molecular Mimicry and Chagas' Disease, p 257-274. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch18

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