Trypanosoma species research and implications (6)Parasitic Infections and Diagnostics (5)Intracranial Aneurysms: Treatment and Complications (4)Estrogen and related hormone effects (4)Vascular Malformations Diagnosis and Treatment (4)
Montoya AL, Carvajal EG, Ortega-Rodriguez U, Estevao IL, Ashmus RA, et al.
Molecules (Basel, Switzerland) •
Chagas disease (CD) is caused by the parasite and affects 6-7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events. The development of safer, more effective therapies is hampered by the lack of biomarker(s) (BMKs) for the early assessment of therapeutic outcomes. The mammal-dwelling trypomastigote parasite stage expresses glycosylphosphatidylinositol-anchored mucins (tGPI-MUC), whose -glycans are mostly branched with terminal, nonreducing α-galactopyranosyl (α-Gal) glycotopes. These are absent in humans, and thus highly immunogenic and inducers of specific CD anti-α-Gal antibodies. In search for α-Gal-based BMKs, here we describe the synthesis of neoglycoprotein NGP11b, comprised of a carrier protein decorated with the branched trisaccharide Galα(1,2)[Galα(1,6)]Galβ. By chemiluminescent immunoassay using sera/plasma from chronic CD (CCD) patients from Venezuela and Mexico and healthy controls, NGP11b exhibited sensitivity and specificity similar to that of tGPI-MUC from genotype TcI, predominant in those countries. Preliminary evaluation of CCD patients subjected to chemotherapy showed a significant reduction in anti-α-Gal antibody reactivity to NGP11b. Our data indicated that NGP11b is a potential BMK for diagnosis and treatment assessment in CCD patients.
Montoya AL, Gil ER, Heydemann EL, Estevao IL, Luna BE, et al.
Molecules (Basel, Switzerland) •
Chagas disease (CD) can be accurately diagnosed by detecting in patients' blood using polymerase chain reaction (PCR). However, parasite-derived biomarkers are of great interest for the serological diagnosis and early evaluation of chemotherapeutic efficacy when PCR may fail, owing to a blood parasite load below the method's limit of detection. Previously, we focused on the detection of specific anti-α-galactopyranosyl (α-Gal) antibodies in chronic CD (CCD) patients elicited by α-Gal glycotopes copiously expressed on insect-derived and mammal-dwelling infective parasite stages. Nevertheless, these stages also abundantly express cell surface glycosylphosphatidylinositol (GPI)-anchored glycoproteins and glycoinositolphospholipids (GIPLs) bearing nonreducing terminal β-galactofuranosyl (β-Gal) residues, which are equally foreign to humans and, therefore, highly immunogenic. Here we report that CCD patients' sera react specifically with synthetic β-Gal-containing glycans. We took a reversed immunoglycomics approach that entailed: (a) Synthesis of GIPL-derived Galβ1,3Manα-(CH)SH (glycan ) and Galβ1,3Manα1,2-[Galβ1,3]Manα-(CH)SH (glycan ); and (b) preparation of neoglycoproteins and , and their evaluation in a chemiluminescent immunoassay. Receiver-operating characteristic analysis revealed that can distinguish CCD sera from sera of healthy individuals with 85.3% sensitivity and 100% specificity. This suggests that Galβ1,3Manα1,2-[Galβ1,3]Manα is an immunodominant glycotope and that could potentially be used as a novel CCD biomarker.