Sulfates are main targets of immune responses to cruzipain in immunized mice and chronic chagasic patients.

D. M. ACOSTA; M.I. ESTEVA; S.A. LAUCELLA; A.S. COUTO; V.G. DUSCHAK

Hamburgo-Alemania

Congreso; Molecular Life Sciences 2007; 2007

GMB

SULFATES ARE MAIN TARGETS OF IMMUNE RESPONSES TO CRUZIPAIN IN IMMUNIZED MICE AND CHRONIC CHAGASIC PATIENTS.   D.M. Acosta a, M.I. Esteva a, S.A. Laucella a, A.S. Couto b  and V.G. Duschak a aDepartamento de Investigación, Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben”, ANLIS-Malbrán, Ministerio de Salud; bCIHIDECAR (CONICET) Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.   Trypanosoma cruzi, the causative agent of Chagas disease or Trypanosomiasis Americana, contains a major cysteine proteinase, cruzipain, with an unusual C-terminal domain (C-T). Recently, we have reported the presence of sulfate groups in N-linked oligosaccharide chains on the unique N-glycosylation site of this domain. The humoral immune responses to sulfated moieties on cruzipain were evaluated in sera from mice immunized with purified cruzipain and the C-Terminal domain prior and after desulfation treatment. The levels of total IgG specific for cruzipain were significantly lower in mice immunized with the sulfate-depleted C-T domain of this glycoprotein compared to those immunized with untreated C-T. The humoral response to sulfates on cruzipain or C-T was mainly IgG2b, whereas IgG1 levels were not related to sulfate groups and IgG3 was undetectable. Interestingly, when either desulfated Cz or desulfated C-T were used as immunogens, the IgG2b reactivity was completely abolished, highlighting these structures as main targets for the IgG2b isotype response. When the humoral immune response to sulfated epitopes on cruzipain was evaluated in sera from chronic Chagas disease patients, the levels of IgG and IgG2 antibodies specific for sulfated epitopes were significantly higher in subjects in the early stages of chronic Trypanosoma cruzi infection compared to those with severe cardiac dysfunction. This is the first report showing that sulfate-bearing glycoproteins in Trypanosomatids, are able to elicit humoral immune responses. Moreover, B-cell responses specific for sulfated epitopes were associated with less severe clinical status in the natural course of T. cruzi infection.