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Probing for Trypanosoma cruzi Cell Surface Glycobiomarkers for the Diagnosis and Follow-Up of Chemotherapy of Chagas Disease

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Book cover Coupling and Decoupling of Diverse Molecular Units in Glycosciences

Abstract

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease in humans. Linear and branched O-glycans with non-reducing, terminal α-galactosyl (α-Gal) glycotopes located on cell surface glycosylphosphatidylinositol (GPI)-anchored mucins of the infective trypomastigote form of the parasite are foreign to humans and elicit high levels of anti-α-Gal antibodies in Chagas disease patients (Ch anti-α-Gal antibodies). These antibodies have the capability to lyse the parasite in a complement-dependent or -independent manner. Ch anti-α-Gal antibodies have a considerably higher reactivity to the parasitic surface α-Gal glycotopes than the normal human serum (NHS) anti-α-Gal antibodies, which are present in every healthy human being. A series of ten mercaptopropyl saccharides with α-Gal moieties at the non-reducing end, all connected to another galactose unit, and five non-α-Gal-containing glycan controls were synthesized, and conjugated to maleimide-derivatized bovine serum albumin. This produced neoglycoproteins (NGPs), which were assembled into glycoarrays for the interrogation with sera of chronic Chagas disease patients and healthy individuals using chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA). This study identified the terminal Galα(1,3)Galβ disaccharide as an immunodominant T. cruzi glycotope and biomarker, which shows a considerable binding differential between Ch and NHS anti-α-Gal antibodies. Therefore, this glycotope is suitable for the diagnosis of Chagas disease, and could also be potentially used for follow-up studies for the effectiveness of chemotherapy in Chagas disease patients.

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Acknowledgements

This work was supported by NIH grants R21AI07961801A1 and 1R21AI115451-01 (to ICA and KM) and Robert J. Kleberg Jr. and Helen C. Kleberg Foundation grants (to ICA, John VandeBerg, and KM). RAA is thankful for a Graduate Teaching Fellowship in K-12 Education (NSF grant DGE 0538623), NSS and AP for “Bridge to the Doctorate” scholarships (NSF grants HRD-1139929 and HRD-083295), and EYM for a MARC scholarship (NIH grant 5T34GM008048). ICA and CRNB were, respectively, Special Visiting Researcher and Visitor Ph.D. (Sandwich) Scholar of the Science Without Borders Program, Brazil. AFM is supported by the CNPq grant # 470737/2013-1. LI, MG and JG receive financial research support from the Generalitat de Catalunya (grant 2009SGR385). We are grateful to the Biomolecule Analysis Core Facility (BACF) at the University of Texas at El Paso (UTEP) for the access to several instruments used in this study. The BACF is supported by the grant # 2G12MD007592 (to Robert A. Kirken) from the National Institutes on Minority Health and Health Disparities (NIMHD), a component of the NIH.

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Authors and Affiliations

  1. Department of Chemistry, University of Texas at El Paso, El Paso, TX, 79968, USA

    Nathaniel S. Schocker, Roger A. Ashmus, Erika Y. Monroy, Andrew Pardo & Katja Michael

  2. Border Biomedical Research Center, Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, 79968, USA

    Susana Portillo, Carlos R. N. Brito, Igor E. Silva, Yanira Cordero Mendoza, Alexandre F. Marques & Igor C. Almeida

  3. Department of Parasitology, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil

    Carlos R. N. Brito & Alexandre F. Marques

  4. Barcelona Institute for Global Health (ISGlobal), Hospital Clinic—Universitat de Barcelona, 08036, Barcelona, Spain

    Luis Izquierdo, Montserrat Gállego & Joaquim Gascon

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  1. Nathaniel S. Schocker
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  2. Susana Portillo
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  13. Igor C. Almeida
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Correspondence to Igor C. Almeida or Katja Michael .

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Editors and Affiliations

  1. Pharmaceutical Sciences Department, Wilkes University, Wilkes-Barre, Pennsylvania, USA

    Zbigniew J. Witczak

  2. Pharmaceutical Sciences Department, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, Pennsylvania, USA

    Roman Bielski

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Schocker, N.S. et al. (2018). Probing for Trypanosoma cruzi Cell Surface Glycobiomarkers for the Diagnosis and Follow-Up of Chemotherapy of Chagas Disease. In: Witczak, Z., Bielski, R. (eds) Coupling and Decoupling of Diverse Molecular Units in Glycosciences. Springer, Cham. https://doi.org/10.1007/978-3-319-65587-1_9

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