Chagas disease (CD) is a neglected tropical disease caused by the protozoan parasite, Trypanosoma cruzi, that affects millions of people worldwide and is becoming an increasingly public health threat to the U.S. The cell surface of the parasite infective trypomastigote stage is densely coated with mucin-like glycoproteins (tGPI-mucins) comprising α-galactopyranosyl (α-Gal)-containing O-linked glycans, which are highly immunogenic to humans and Old-World nonhuman primates. The exact structures of most of these glycans remain elusive, but it is known that terminal, nonreducing α-Gal moieties and branching within the glycans are predominant. Based on preliminary data, we hypothesize that the branched trisaccharide Galα(1,6)[Galα(1,2)]Galβ could be the terminal portion of larger tGPI-mucin O-glycans. Protective T. cruzi-specific anti-α-Gal antibodies present in the sera of both acute and chronic CD patients (CD anti-α-Gal Abs) strongly bind to that trisaccharide, suggesting that it could be one of the immunodominant glycotopes present on the trypomastigote cell surface. Here, we have evaluated the neoglycoprotein NGP11B, which consists of multiple copies of Galα(1,6)[Galα(1,2)]Galβ, chemically conjugated to bovine serum albumin, as a biomarker in a chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) to diagnose CD and assess the efficacy of benznidazole in chronically infected adults from endemic and nonendemic areas. We found that NGP11B was able to diagnose CD in the great majority of the patients with a clear differential immunoreactivity between CD patients and healthy individuals, which demonstrates that CD anti-α-Gal Abs recognize the α-Gal-containing glycotope in NGP11B with great specificity. Furthermore, CD patients who have completed benznidazole treatment show decreasing CD anti-α-Gal Ab levels over time toward seroconversion. This work provides insights into the immunoreactivity of NGP11B as a potential biomarker for diagnosis and early assessment of chemotherapeutic outcomes in CD.

Evaluation of a synthetic branched α-Gal-containing trisaccharide as a potential biomarker for the diagnosis and follow-up of chemotherapy of Chagas disease

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.