A cross section of a human population (501 individuals)

No abstract

Monoclonal antibodies were raised against a recombinant ribosomal P2β protein of Trypanosoma cruzi. One of these reacted with the C terminus of this protein (peptide R13, EEEDDDMGFGLFD) and epitope mapping confirmed that this epitope was the same as the one defined by the serum of immunized mice, and similar to the previously described chronic Chagas' heart disease (cChHD) anti‐P epitope. Western blotting showed that the monoclonal antibody recognized the parasite ribosomal P proteins, as well as the human ribosomal P proteins. Electron microscopy showed that it stained different structures in parasite and human cells. Interestingly, surface plasmon resonance measurements indicated that the affinity for the parasite ribosomal P protein epitope (R13) was five times higher than for its human counterpart (peptide H13, EESDDDMGFGLFD). Since the human epitope contained an acidic region (EESDD) similar to the AESDE peptide recognized by cChHD patients in the second extra‐cellular loop of the human β1‐adrenergic receptor, the biological activity of the antibody was assessed on neonatal rat cardiomyocytes in culture. The monoclonal antibody had an agonist‐like effect. These results, together with the fact that the monoclonal reacted in Western blots with the different isoforms of the heart β1‐adrenergic receptor, confirm the possible pathogenic role of antibodies against the parasite ribosomal P protein based on their cross‐reaction with the human β1‐adrenergic receptor.

A large field study has been performed in the Cochabamba region of Bolivia with the aim of comparing the polymerase chain reaction (PCR) with other diagnosis methods for Chagas' disease. The amplification of Trypanosoma cruzì-specific kinetoplast DNA sequences in blood samples was compared with classical serological methods, specific IgM detection and direct parasite visualization for 268 school children in a single village where Chagas' disease transmission is active. cardiac and/or digestive manifestations, the latter with pathological dilatation of the colon andor esophagus optical and electronic microscopy show the presence of inflammatory infiltrates, with degeneration of m hand, examination of esophageal tissues of Chagas' disease patients with the digestive clinical form have hithe to demonstrate a close correlation between the megaesophagus pathology and the presence of Z cruzi.. We have

Antibodies against the Trypanosoma cruzi ribosomal P2␤ protein (TcP2␤) have been associated with the chronic cardiac pathology of Chagas' disease in humans. Using synthetic peptides spanning the entire TcP2␤ molecule, we investigated their epitope recognition by antibodies from mice chronically infected with T. cruzi and from mice immunized with two recombinant TcP2␤s. We found clear differences in epitope recognition between antibodies from T. cruzi-infected mice and mice immunized with two different recombinant TcP2␤s associated with different schedules of immunization. Major epitopes recognized by antibodies from mice immunized with recombinant glutathione S-transferase (GST) or histidine (Hist) fusion TcP2␤ (GST-TcP2␤ or HistTcP2␤) are located in the central and hinge regions of the molecule. Nevertheless, mice immunized with Hist-TcP2␤ were also able to elicit antibodies against the TcP2␤ C terminus, a region which is highly conserved in both T. cruzi and mammal ribosomal P proteins. Strikingly, antibodies from infected animals recognized only the TcP2␤ C terminus. By using these antisera with distinct profiles of epitope recognition, it could be shown that only C terminus-specific antibodies were able to increase the beating frequency of cardiomyocytes from neonatal rats in vitro by selective stimulation of the ␤1-adrenergic receptor. Thus, antibodies against the TcP2␤ C terminus elicited in the absence of infection are able to modulate a functional activity of host cells through a molecular mimicry mechanism.