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Big is not better: Comparing two alpha-Gal-bearing glycotopes in neoglycoproteins as biomarkers for Leishmania (Viannia) braziliensis infection.
Montoya, Alba L; Gil, Eileni R; Vinales, Irodiel; Estevao, Igor L; Taboada, Paola; Torrico, Mary Cruz; Torrico, Faustino; Marco, Jorge Diego; Almeida, Igor C; Michael, Katja.
Afiliação
  • Montoya AL; Department of Chemistry and Biochemistry, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, USA.
  • Gil ER; Department of Chemistry and Biochemistry, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, USA.
  • Vinales I; Department of Chemistry and Biochemistry, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, USA.
  • Estevao IL; Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, USA.
  • Taboada P; Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, USA.
  • Torrico MC; Universidad Mayor de San Simón, Faculty of Medicine, and Fundación CEADES, Cochabamba, Bolivia.
  • Torrico F; Universidad Mayor de San Simón, Faculty of Medicine, and Fundación CEADES, Cochabamba, Bolivia.
  • Marco JD; Universidad Nacional de Salta (UNSa)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Patología Experimental, Facultad de Ciencias de la Salud, Universidad Nacional de Salta, Salta, Argentina.
  • Almeida IC; Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, USA. Electronic address: icalmeida@utep.edu.
  • Michael K; Department of Chemistry and Biochemistry, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, USA. Electronic address: kmichael@utep.edu.
Carbohydr Res ; 536: 109015, 2024 Feb.
Article em En | MEDLINE | ID: mdl-38198982
ABSTRACT
The protozoan parasite Leishmania (Viannia) braziliensis is among Latin America's most widespread Leishmania species and is responsible for tegumentary leishmaniasis (TL). This disease has multiple clinical presentations, with cutaneous leishmaniasis (CL) being the most frequent. It manifests as one or a few localized skin ulcers, which can spread to other body areas. Hence, early diagnosis and treatment, typically with pentavalent antimonials, is critical. Traditional diagnostic methods, like parasite culture, microscopy, or the polymerase chain reaction (PCR) for detection of the parasite DNA, have limitations due to the uneven distribution of parasites in biopsy samples. Nonetheless, studies have revealed high levels of parasite-specific anti-α-Gal antibodies in L. (V.) braziliensis-infected patients. Previously, we demonstrated that the neoglycoprotein NGP28b, consisting of the L. (Leishmania) major type-2 glycoinositolphospholipid (GIPL)-3-derived trisaccharide Galpα1,6Galpα1,3Galfß conjugated to bovine serum albumin (BSA) via a linker, acts as a reliable serological biomarker (BMK) for L. (V.) braziliensis infection in Brazil. This indicates the presence of GIPL-3 or a similar structure in this parasite, and its terminal trisaccharide either functions as or is part of an immunodominant glycotope. Here, we explored whether extending the trisaccharide with a mannose unit would enhance its efficacy as a biomarker for the serological detection of L. (V.) braziliensis. We synthesized the tetrasaccharide Galpα1,6Galpα1,3Galfß1,3Manpα(CH2)3SH (G31SH) and conjugated it to maleimide-functionalized BSA to afford NGP31b. When we assessed the efficacy of NGP28b and NGP31b by chemiluminescent enzyme-linked immunosorbent assay on a cohort of CL patients with L. (V.) braziliensis infection from Bolivia and Argentina against a healthy control group, both NGPs exhibited similar or identical sensitivity, specificity, and accuracy. This finding implies that the mannose moiety at the reducing end is not part of the glycotope recognized by the parasite-specific anti-α-Gal antibodies in patients' sera, nor does it exert a relevant influence on the terminal trisaccharide's conformation. Moreover, the mannose does not seem to inhibit glycan-antibody interactions. Therefore, NGP31b is a viable and dependable BMK for the serodiagnosis of CL caused by L. (V.) braziliensis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leishmania braziliensis / Leishmaniose Cutânea Tipo de estudo: Screening_studies Limite: Humans País/Região como assunto: America do sul / Brasil Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leishmania braziliensis / Leishmaniose Cutânea Tipo de estudo: Screening_studies Limite: Humans País/Região como assunto: America do sul / Brasil Idioma: En Ano de publicação: 2024 Tipo de documento: Article