Response to Hyland and Engman: Chagas disease - the solutions lie ahead

My recent Trends in Parasitology article [1xWhere do we stand on the autoimmunity hypothesis of Chagas disease?. Kierszenbaum, F. Trends Parasitol. 2005; 21: 513–516Abstract | Full Text | Full Text PDF | PubMed | Scopus (62)See all References[1] required considerable condensation of the available information and commentary. I suspect that this might have lead to the misinterpretation of some of my views by Hyland and Engman (in this issue of Trends in Parasitology) because I do not particularly disagree with their comments.In an earlier review about the autoimmunity hypothesis of Chagas disease [2xChagas' disease and the autoimmunity hypothesis. Kierszenbaum, F. Clin. Microbiol. Rev. 1999; 12: 210–223PubMedSee all References[2], I included a section that summarized non-autoimmune mechanisms described for the development of tissue lesions in chagasic mammals. Some of these are listed in the letter by Hyland and Engman. I closed that section by stating that ‘it should be emphasized that there is no claim or evidence that any of these mechanisms, even if conclusively documented, would be exclusively responsible for tissue damage in Chagas disease’ [2xChagas' disease and the autoimmunity hypothesis. Kierszenbaum, F. Clin. Microbiol. Rev. 1999; 12: 210–223PubMedSee all References[2]. This statement is as true today as one contending that a crucial role of autoimmunity in the pathogenesis of Chagas disease remains to be demonstrated conclusively. It is hard to believe that anything I wrote in the short review, or anywhere else, could be interpreted as meaning anything other than that Chagas disease is not a single clinical entity. In fact, my comments about, and references to, studies comparing data from cases with either overt or asymptomatic Chagas disease implied complexity and diversity in chagasic pathology.The opinion of Hyland and Engman might be different from mine in terms of the appreciation of the impact that the autoimmunity hypothesis of Chagas disease has had on pursuing means to prevent and cure this disorder. But I was among those researching Chagas disease in the 1970s and I noted with concern how the funding for studies aimed at developing vaccines against Trypanosoma cruzi virtually dried up after the publication of early reports that suggested a possible role for autoimmunity in Chagas disease pathogenesis. For reasons described in my recent reviews [1xWhere do we stand on the autoimmunity hypothesis of Chagas disease?. Kierszenbaum, F. Trends Parasitol. 2005; 21: 513–516Abstract | Full Text | Full Text PDF | PubMed | Scopus (62)See all References, 2xChagas' disease and the autoimmunity hypothesis. Kierszenbaum, F. Clin. Microbiol. Rev. 1999; 12: 210–223PubMedSee all References, 3xViews on the autoimmunity hypothesis for Chagas disease pathogenesis. Kierszenbaum, F. FEMS Immunol. Med. Microbiol. 2003; 37: 1–11Crossref | PubMed | Scopus (39)See all References], the autoimmunity hypothesis also led to diminished interest in pursuing chemotherapy against T. cruzi. The development of vaccines and chemotherapy should be encouraged, regardless of whether autoimmunity is a major contributor to Chagas disease pathology, and some movement in this direction is beginning to occur.I hope that Hyland and Engman do not believe that I have claimed that autoimmunity must result from molecular mimicry or that a vaccine must contain mimic antigens because I have never made these claims. My views and criticisms about the experiments and inferences of others who have suggested a role for molecular mimicry in chagasic autoimmunity have been published [1xWhere do we stand on the autoimmunity hypothesis of Chagas disease?. Kierszenbaum, F. Trends Parasitol. 2005; 21: 513–516Abstract | Full Text | Full Text PDF | PubMed | Scopus (62)See all References, 2xChagas' disease and the autoimmunity hypothesis. Kierszenbaum, F. Clin. Microbiol. Rev. 1999; 12: 210–223PubMedSee all References, 3xViews on the autoimmunity hypothesis for Chagas disease pathogenesis. Kierszenbaum, F. FEMS Immunol. Med. Microbiol. 2003; 37: 1–11Crossref | PubMed | Scopus (39)See all References, 4xAutoimmunity in Chagas' disease. Kierszenbaum, F. J. Parasitol. 1986; 72: 201–211Crossref | PubMedSee all References] and speak for themselves.Several articles by Engman and colleagues have been published regarding myosin-directed autoimmunity in experimental Chagas disease (for review, see Refs [5xPathogenesis of Chagas heart disease: role of autoimmunity. Engman, D.M. and Leon, J.S. Acta Trop. 2002; 81: 123–132Crossref | PubMed | Scopus (84)See all References, 6xThe significance of autoimmunity in the pathogenesis of Chagas heart disease. Leon, J.S. and Engman, D.M. Front. Biosci. 2003; 8: e315–e322Crossref | PubMedSee all References]). No-one could describe better than him how much work remains to be done before a primary role for this particular autoreactivity in chagasic pathology can be accepted without reservation. The need for additional work to assign autoimmunity its proper place and context in Chagas disease pathogenesis is one with which I assume we all agree. We have waited long enough.I thank Hyland and Engman for their complimentary comments about my article and for re-emphasizing the points I raised about further efforts that must be undertaken. If there were any remaining disagreement, it would not alter the fact that I share with Hyland and Engman a desire to learn more about the pathogenesis of Chagas disease and to achieve its eradication.