Unraveling the Mechanism of Chagas

The Significance of Autoimmunity in the Pathogenesis of Chagas Heart Disease

Juan S. Leon and David M. Engman

May, 2003

Frontiers in Bioscience

Although we have been studying it for nearly half a century, we are still unsure of the exact mechanism of Chagas heart disease. One of the long standing hypotheses is that it could be an autoimmune disease. This hypothesis came from early observations of cardiac pathology and the discovery of antibodies that were reactive to the T. cruzi parasite as well as host proteins in patients with chronic Chagas heart disease. It is important that we figure out whether or not it is an autoimmune disease because it would change the way we treat the disease; if it is an autoimmune disease treatments must be targeted towards autoimmune mechanisms and not just the parasite.

It is clear that autoimmunity can be induced by T. cruzi in humans and animals but according to the authors there is no proof that autoimmunity directly contributes to Chagas heart disease. Several observations allow for other possibilities. One of these is the possibility that it is not live parasites that cause the inflammation. It may be that antigens from destroyed T. Cruzi remain in the heart tissue and cause ongoing inflammation. Other possibilities include that the Chagas parasite causes tissue ischemia and subsequent inflammation, or that it is caused an overly aggressive anti-parasite inflammatory response to the chronic presence of the parasite. There is nothing to disprove the autoimmunity hypothesis but there are also still many other possible hypotheses that need to be ruled out.

According to the authors there is “strong evidence in support of the hypothesis that Chagas disease can be explained by persistent parasite and anti-parasite immunity.” Although there is strong evidence that the parasite can induce autoimmunity the authors make the specific point that there is no well documented proof that this autoimmunity is “pathogenic” meaning that it might not be causing Chagas heart disease. One of the pieces of evidence against the autoimmunity hypothesis is that immunosuppressants have been documented to increase mortality, instead of decreasing it as one would expect. Immunosuppressants might simply make it easier for the parasites to cause disease. Furthermore anti T. cruzi chemotherapy has been shown to reduce heart disease. One interesting suggestion, based on the fact that Chagas disease outcomes are so varied, is that “T. cruzi may induce autoimmunity and/or disease depending on host immunogenetics and parasite genetics” which may make the particular strain autoimmunity-inducing or not.

http://cruzi.pathology.northwestern.edu/engmanlab/pdf/ReprintFBS.pdf