EPITOPES COMMON TO TRYPANOSOMA-CRUZI AND MAMMALIAN-TISSUES ARE RECOGNIZED BY SERA FROM CHAGAS-DISEASE PATIENTS - PROGNOSIS VALUE IN CHAGAS-DISEASE

Monoclonal antibodies (MoAbs) raised against Trypanosoma cruzi microso mal fraction (Me) and cross-reactive with mammalian tissues were used to evaluate the ability of crossreactive T. cruzi antigens to induce a n immune response in Chagas' disease. Thus, we studied the ability of sera from Chagas' disease patients (CDP) with different degrees of car diac dysfunction to block the immune recognition of these MoAb to the target antigen determining for each serum an inhibition index (II). By means of this approach we inferred that blocking of monoclonal antibo dy binding to T. cruzi microsomes by subjects' serum represents antibo dies with the same reactivity. After serological and medical examinati ons, individuals were separated into the following groups: Chagas' dis ease patients without manifest cardiac involvement (CDP-0), CDP with s uspected or borderline cardiac disease (CDP-1), CDP with moderate myoc ardial dysfunction (CDP-2), CDP with overt cardiac dysfunction (CDP-3) and controls including healthy subjects (HS) and patients with idiopa thic myocarditis (IMP). The reactivity between MoAb 5F2 and its target antigen was significantly (p<0.05) inhibited by sera from CDP irrespe ctive of the clinical stage [CDP: n = 46, 50 +/- 20, mean II +/- SD; c ontrol: n = 16, 18 +/- 8]. Moreover, 5F2 was able to distinguish (p<0. 05) sera from CDP with mild disease (CDP clinical grade 0/1: n = 26, 3 4 +/- 18) from that of CDP with severe disease (CDP clinical grade 2/3 : n = 20, 67 +/- 7). Moreover, the inhibitory capacity of sera from as ymptomatic CDP (CDP-0) correlated with patients age (r = 0.66, p<0.05) . CDP-0 below or equal 40 years of age had results (n = 15, 25 +/- 13) comparable (p > 0.05) to that of controls while mean inhibition of CD P-0 over 40 years of age (n = 5, 60 +/- 5) was indistinguishable (p > 0.05) from that of patients with severe disease. Competitive assay wit h MoAb 5A9B11 also showed significant differences (p<0.05) between ser a from CDP (n = 46, 46 +/- 24) and controls(n = 13, 5 +/- 5). On the c ontrary, the differences observed between CDP with different cardiac i nvolvement was not significant (mild: n=26, 31 +/- 22; severe: n = 20, 66 +/- 11). However a thorough study of data from asymptomatic group sera revealed the existence of two levels of reactivity, with low and high capacity to inhibit the reaction of 5A9B11 against Me. On the con trary, CDP sera showed a blocking activity for 1A10C11 comparable to t hat of controls (CDP: n = 25, 19 +/- 9; control: n = 12, 14 +/- 6). So me cross-reactive MoAbs recognized epitopes partially composed of carb ohydrates. Interestingly, 5F2 and 5A9B11 epitopes did not appear to ha ve carbohydrates moieties. In summary, immunoinibition assays revealed differences in the immune response of chronic chagasic patients again st parasite epitopes. These results have opened the possibility to ide ntify a prognosis marker of the disease suggesting the clinical utilit y of monitoring levels of these anti-Me antibodies in patients with ch ronic Chagas' disease.