Glycoconjugates of Trypanosoma cruzi: A 74 kD antigen of trypomastigotes specifically reacts with lytic anti‐α‐galactosyl antibodies from patients with chronic Chagas disease

Abstract

Protective, lytic antibodies are believed to be correlated with active Trypanosoma cruzi infection. In patients with chronic infection, antibodies lysing trypomastigote forms recognize chiefly alpha-galactosyl structures at the parasite surface. The target molecules on cell-derived trypomastigotes that react with anti-alpha-galactosyl antibodies (anti-Gal) from patients with chronic Chagas disease were investigated. Glycoconjugates were isolated from trypomastigotes and shown to absorb purified Chagasic (Ch) anti-Gel effectively as well as lytic antibodies from Ch sera. Active fractions were F2 (74 kD and 95.6 kD) and F3 (120-200 kD). A differential reactivity with antibodies from untreated Ch patients (trypanolytic) and from treated, presumably cured, individuals (not trypanolytic) was evident using F2 and F3 antigenic fractions. No cross-reactivity with heterologous sera (other infections) was observed. The F2 glycoconjugate (mostly 74 kD) can be used in the diagnosis of active Chagas infection, replacing the quantitative determination of complement-mediated lysis. With the present sample of patients' sera and normal human sera, it showed 100% sensitivity and specificity.

Intraspecies Variation in Trypanosoma cruzi GPI-Mucins: Biological Activities and Differential Expression of α-Galactosyl Residues

“…Because of the fact that mostly T. cruzi glycoconjugates are on the external surface of cells or secreted, they are able to modulate and mediate important cell-cell, cell-matrix, and cell-molecule interactions. 14,51,52,57 Infections and immune responses suffer major interferences and depend on N-and O-linked carbohydrates during innate and adaptive responses. 58 During its life cycle, T. cruzi trypomastigotes are able to release extracellular vesicles containing glycoproteins from the parasite surface.…”

Early, intermediate, and late acute stages in Chagas' disease: a study combining anti-galactose IgG, specific serodiagnosis, and polymerase chain reaction analysis.

“…Two classes of anti-Gal antibodies exists in chagasic patients: low-affinity natural anti-Gal antibodies and high-affinity lytic chagasic anti-Gal antibodies. 30 After specific therapy when lytic antibodies disappear (indicating the end of active infection), only the natural low-affinity antiGal antibodies account for T. cruzi and anti-Gal remaining reactivity in the serum. 31 Since the children studied were not treated, anti-Gal antibodies detected at serum dilution of 1: 5,000 are probably all lytic chagasic anti-Gal antibodies.…”

The Surface Coat of the Mammal-dwelling Infective Trypomastigote Stage of Trypanosoma cruzi Is Formed by Highly Diverse Immunogenic Mucins

“…A thick coat of glycoproteins covers the surface of all these developmental stages (3)(4)(5)(6)(7)(8)(9)(10)(11). The major protein components of this coat have been identified as glycosylphosphatidylinositol (GPI) 1 -anchored molecules enriched in Thr, Ser, and Pro residues that serve as a scaffold for the extensive addition of O-glycans (5, 8 -10, 12).…”

“…Mucins play a key role in parasite protection and infectivity and modulation of the host immune response throughout the T. cruzi life cycle (14 -16). The mucin coat of the cell-derived trypomastigotes (tGPI-mucins) is composed of an undefined mixture of molecules ranging from 60 to 220 kDa (6,7,9) and sharing the stage-specific, sialic acid-containing epitope Ssp-3, critical for mammalian cell attachment/invasion (17,18). tGPI-mucins or their GPI moieties are potent inducers of nitric oxide and pro-inflammatory cytokines by macrophages (15,19).…”

“…tGPI-mucins or their GPI moieties are potent inducers of nitric oxide and pro-inflammatory cytokines by macrophages (15,19). Major protective lytic antibodies directed against ␣-galactosyl epitopes present in tGPI-mucins have been described in sera from chronic Chagas' disease patients (6,7,9,11).…”