Specific Recognition of β-Galactofuranose-Containing Glycans of Synthetic Neoglycoproteins by Sera of Chronic Chagas Disease Patients

Molecules

Igor C. Almeida¹  Cameron C. Ellis¹  Bianca E. Luna¹  Igor L. Estevao¹  Sohan R. Jankuru²  Alba L. Montoya²  Emily L. Heydemann²  Katja Michael²  Eileni R. Gil²  Maria Paola Zago³  Oscar Noya⁴  Belkisyolé Alarcón de Noya⁴ 

[1] Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA;Department of Chemistry and Biochemistry, Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA;Instituto de Patología Experimental, Facultad de Ciencias de la Salud, Universidad Nacional de Salta (UNSa)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Salta 4400, Argentina;Sección de Inmunología, Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela, Caracas 1041-A, Venezuela;

关键词: biomarker;    Chagas disease;    chemiluminescent enzyme-linked immunosorbent assay;    galactofuranose;    neoglycoproteins;    oligosaccharide synthesis;   

DOI  :  10.3390/molecules27020411

来源: DOAJ

【 摘 要 】

Chagas disease (CD) can be accurately diagnosed by detecting Trypanosoma cruzi 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-Galf) residues, which are equally foreign to humans and, therefore, highly immunogenic. Here we report that CCD patients’ sera react specifically with synthetic β-Galf-containing glycans. We took a reversed immunoglycomics approach that entailed: (a) Synthesis of T. cruzi GIPL-derived Galfβ1,3Manpα-(CH₂)₃SH (glycan G29_SH) and Galfβ1,3Manpα1,2-[Galfβ1,3]Manpα-(CH₂)₃SH (glycan G32_SH); and (b) preparation of neoglycoproteins NGP29b and NGP32b, and their evaluation in a chemiluminescent immunoassay. Receiver-operating characteristic analysis revealed that NGP32b can distinguish CCD sera from sera of healthy individuals with 85.3% sensitivity and 100% specificity. This suggests that Galfβ1,3Manpα1,2-[Galfβ1,3]Manpα is an immunodominant glycotope and that NGP32b could potentially be used as a novel CCD biomarker.

【 授权许可】

Unknown