Enabling the serodiagnosis of American tegumentary leishmaniasis using synthetic aminopentyl-galactofuranoside-containing oligosaccharide epitopes

Abstract

The diagnosis of American tegumentary leishmaniasis (ATL), caused primarily by Leishmania braziliensis in Latin America, remains difficult due to the lack of specific serological tools. Here, we report the chemical synthesis and immunological evaluation of five structurally defined galactofuranosyl-containing oligosaccharides that mimic type II glycoinositolphospholipids (GIPLs) found on the parasite surface. The synthetic glycotopes, equipped with a terminal aminopentyl linker, were immobilized onto microarrays and tested against human sera from ATL and Chagas disease (CD) patients, as well as healthy controls. Most IgM antibodies in ATL sera were found recognizing the β-D-Galf-(1 → 3)-α-D-Man-(1 → 3)-D-Man trisaccharide 3, with minimal cross-reactivity to antibodies in CD samples. In contrast, two glycotopes containing terminal α-D-Gal motifs were less selective due to the presence of cross-reactive anti-α-D-Gal antibodies in human sera. Trisaccharide 3 is a promising candidate for ATL serodiagnosis and illustrates the value of synthetic glycan-based tools for the development of diagnostic platforms.