The fundamental nature of Chagas' disease:A view provided by immune responses and idiotypes.

Abstract

Chagas' disease is caused by the protozoan Trypanosoma cruzi which infects 10-15 million people in endemic areas throughout Latin America and is naturally transmitted by insect vectors of the family Reduviidae. Infection can also occur by congenital passage, oral ingestion, laboratory accident, and in organ transplants and blood transfusions. There are 3 life-cycle forms of T. cruzi. Epimastigotes multiply in the midgut of the insect vector, differentiate in the hind-gut into infectious trypomastigotes, patients who die of unrelated causes have identical (but less intense) lesions. Responses against T. cruzi antigens, their immunoregulation, and responses against related idiotypes (Ids) correlate with the presence of the different clinical forms of the infection. Although there are numerous findings of autoimmune lymphocyte and antibody reactivities in chagasic patients, a causal relationship is always difficult to prove. Chagasic patients' peripheral blood mononuclear cells (PBMC) respond to T. cruzi epimastigote antigens (EPI) with varying vigor. Almost all low responders are Cpatients, and their responses are usually augmented by removal of adherent macrophage suppressor cells or the addition of indomethacin. Chronic I-patients are medium or high responders, and exhibit little adherent cell-mediated immunoregulation. Western blotting

Myocardial parasite persistence in chronic chagasic patients.

“…26 The fact that autoimmune responses in patients with chronic disease have been detected as crossreactivity between T. cruzi antigens and host tissues 12 or T. cruzi anti-idiotypic interactions 27 has led several investigators to state that the autoimmune phenomenon occurs in the absence of the parasite, questioning the direct role of T. cruzi in the production of late cardiac injury. 12 However, other investigators have confirmed the presence of a portion of the parasite genome or T. cruzi amastigotes in the myocardium of autopsied patients with chronic disease using the PAP and PCR techniques, respectively.…”

Self and Nonself Stimulatory Molecules Induce Preferential Expansion of CD5+ B Cells or Activated T Cells of Chagasic Patients, Respectively

“…Determining whether these cell populations are preferentially responsive to parasite antigens or to T. cruzi-related self stimuli such as cross-reactive idiotypes [9,10] would provide insights into the possible involvement of these cells in autoimmune processes in Chagas disease. Although some involvement of anti-host reactions in Chagas' disease is generally accepted by many researchers, it is critical to remember that whatever mechanisms participate in pathology, they also depend on the initial infection and exist in the presence of a continued low grade infection [11].…”

Humoral nitric oxide levels and antibody immune response of symptomatic and indeterminate Chagas' disease patients to commercial and autochthonous Trypanosoma cruzi antigen.

“…Many studies of Chagas' disease, including immunologic investigations, have failed to differentiate between asymptomatic infection and chronic disease. 9,[29][30][31] In this report, we observed that symptomatic patients showed statistically different antibody levels than asymptomatic individuals when determined by ELISA using autochthonous antigen (P Ͻ 0.05). This difference was not observed with the commercial antigen preparation.…”