A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease.

Autor: Montoya AL; Department of Chemistry and Biochemistry, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Carvajal EG; Department of Chemistry and Biochemistry, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Ortega-Rodriguez U; Department of Biological Sciences, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Estevao IL; Department of Biological Sciences, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Ashmus RA; Department of Chemistry and Biochemistry, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Jankuru SR; Department of Chemistry and Biochemistry, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Portillo S; Department of Biological Sciences, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Ellis CC; Department of Biological Sciences, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Knight CD; Department of Biological Sciences, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Alonso-Padilla J; Barcelona Institute for Global Health (ISGlobal), 08003 Barcelona, Spain.; Consorcio Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), 28029 Madrid, Spain., Izquierdo L; Barcelona Institute for Global Health (ISGlobal), 08003 Barcelona, Spain.; Consorcio Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), 28029 Madrid, Spain., Pinazo MJ; Barcelona Institute for Global Health (ISGlobal), 08003 Barcelona, Spain.; Consorcio Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), 28029 Madrid, Spain.; Hospital Clínic de Barcelona, 08036 Barcelona, Spain., Gascon J; Barcelona Institute for Global Health (ISGlobal), 08003 Barcelona, Spain.; Consorcio Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), 28029 Madrid, Spain.; Hospital Clínic de Barcelona, 08036 Barcelona, Spain., Suarez V; Department of Biological Sciences, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Watts DM; Department of Biological Sciences, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Malo IR; Centro Regional de Investigación en Salud Pública, Instituto Nacional de Salud Pública, Tapachula 30700, Chiapas, Mexico., Ramsey JM; Centro Regional de Investigación en Salud Pública, Instituto Nacional de Salud Pública, Tapachula 30700, Chiapas, Mexico., Alarcón De Noya B; Sección de Inmunología, Instituto de Medicina Tropical, Universidad Central de Venezuela, Caracas 1041, Venezuela., Noya O; Seccion de Biohelmintiasis, Instituto de Medicina Tropical, Universidad Central de Venezuela, Caracas 1041, Venezuela., Almeida IC; Department of Biological Sciences, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA., Michael K; Department of Chemistry and Biochemistry, Border Biochemical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2022 Sep 05; Vol. 27 (17). Date of Electronic Publication: 2022 Sep 05.
DOI: 10.3390/molecules27175714
Abstrakt: Chagas disease (CD) is caused by the parasite Trypanosoma cruzi 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 O -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.
Databáze: MEDLINE
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