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Chapter: Essential Clinical Immunology: Immunological Aspects of Cardiac Disease

Autoimmunity and Pathogenesis of Chagas’ Disease

The theory of autoimmunity leading to damage in chronic Chagas’ disease is sup-ported by a number of observations.

AUTOIMMUNITY AND PATHOGENESIS OF CHAGAS’ DISEASE

 

The theory of autoimmunity leading to damage in chronic Chagas’ disease is sup-ported by a number of observations. First, few parasites can be demonstrated in the inflammatory lesions by conventional his-tological study. This observation suggests the disease may not be driven solely by reac-tion to the parasite. Second, only 10 percent to 30 percent of chronically infected people develop Chagas’ disease, although most can be shown to have chronic parasitemia. This suggests that, in addition to chronic T. cruzi infection, some other factor(s) determines which individual develops dis-ease. Susceptibility to autoimmune disease could be the host factor that determines who develops disease. Third, chronic Cha-gas’ disease is very organ specific, gener-ally limited to the heart, nervous tissues, or innervation of the gut. Since the parasite can reside in almost any cell type, the organ specificity of Chagas’ disease suggests that additional specificity of Chagas’ disease is imposed during infection, perhaps by the particular autoimmune response that is generated by chronic T. cruzi infection. Fourth, the long lag time from infection to disease could be necessary to generate dis-ease by autoimmunity. Fifth, the presence of autoimmune T cells and antibodies in infected individuals, especially when they are associated with disease, is evidence that autoimmunity may play a role in pathogenesis. It should also be noted that each of these properties of chronic Chagas’ disease could be due to parasite-directed pathogenesis, as discussed below.

 

Autoimmune antibodies are easily demonstrated in T. cruzi-infected indi-viduals. Antibodies to myocardium and nervous tissues are found in high levels in persons and mice infected with T. cruzi compared with those that are not. Since the myocardium and nervous tissues are key organs that are damaged in chronic Cha-gas’ disease, finding antibodies to these tissues could mean that these antibodies cause autoimmune damage to these tis-sues. As an alternative, antigens from myo-cardium and nervous tissues are probably exposed by the damage of infection of these organs, and antibodies may be generated to these tissues without being pathogenic.

Many of the autoantibodies found in the sera of T. cruzi–infected persons and mice are so-called natural autoantibodies, which can be found in low levels in the serum of normal humans and mice. The “natural autoantibodies” are directed against pro-teins that are highly conserved in evolu-tion and are not necessarily an indication of autoimmune disease. The high levels of natural autoantibodies after T. cruzi infec-tion may be the result of the polyclonal lym-phocytic proliferative response that occurs during acute infection. Levels of natural autoantibodies do not correlate with dis-eases in individuals who are chronically infected with T. cruzi.


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Essential Clinical Immunology: Immunological Aspects of Cardiac Disease : Autoimmunity and Pathogenesis of Chagas’ Disease |


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