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SERODIAGNOSIS AND THERAPEUTIC MONITORING OF NEW-WORLD TEGUMENTARY LEISHMANIASIS USING SYNTHETIC TYPE-2 GLYCOINOSITOLPHOSPHOLIPID-BASED NEOGLYCOPROTEINS
Leishmaniose tegumentar
Biomarcadores de diagnóstico e prognóstico
Neoglicoproteínas α-Gal
Anticorpos anti-α-Gal
Tegumentary leishmaniasis
Diagnostic and prognostic biomarkers
α-Gal neoglycoproteins
Anti-α-Gal antibodies
Tegumentary leishmaniasis
Biomarcadores
Diagnóstico
Prognóstico
Glicoproteínas
Anticorpos
Autor
Afiliación
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Department of Chemistry and Biochemistry, Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais. Salvador, BA, Brasil.
Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais. Salvador, BA, Brasil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brasil.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Department of Chemistry and Biochemistry, Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais. Salvador, BA, Brasil.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Department of Chemistry and Biochemistry, Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais. Salvador, BA, Brasil.
Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais. Salvador, BA, Brasil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brasil.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Department of Chemistry and Biochemistry, Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais. Salvador, BA, Brasil.
Department of Biological Sciences. Border Biomedical Research Center. The University of Texas at El Paso. El Paso, Texas, U.S.A.
Resumen en ingles
American tegumentary leishmaniasis (TL) caused by Leishmania braziliensis is characterized by a spectrum of clinical presentations, ranging from localized cutaneous ulcers (CL), mucosal (ML), or disseminated (DL) disease, to a subclinical (SC) asymptomatic form. Current diagnosis based on parasite culture and/or microscopy lacks sensitivity and specificity. Previous studies showed that patients with CL and ML have very high levels of Leishmania-specific anti-α-Gal antibodies. However, the native parasite α-Gal glycotope(s) is(are) still elusive, thus they have not yet been explored for a more accurate TL diagnosis. Using a chemiluminescent immunoassay, we evaluated the seroreactivity of TL patients across its clinical spectrum, and of endemic (EC) and nonendemic healthy controls (NEC) against three synthetic neoglycoproteins (NGP29b, NGP30b, and NGP28b), respectively comprising the L. major-derived type-2 glycoinositolphospholipid (GIPL)-1 (Galfβ1,3Manα), GIPL-2 (Galα1,3Galfβ1,3Manα), and GIPL-3 (Galα1,6Galα1,3Galfβ) glycotopes. Contrary to NGP29b and NGP30b, NGP28b exhibited high sensitivity and specificity to a CL serum pool. More importantly, NGP28b reacted strongly and specifically with individual sera from distinct clinical forms of TL, especially with SC sera, with 94% sensitivity and 97% specificity, by post-two-graph receiver-operating characteristic curve analysis. Contrary to NGP29b, NGP28b showed low cross-reactivity with Chagas disease and control (NEC/EC) sera. Additionally, seroreactivity of CL patients against NGP28b was significantly decreased after successful chemotherapy, indicating that L. braziliensis-specific anti-α-Gal antibodies may serve as an early biomarker of cure in CL. Our data also points towards the applicability of L. major type-2 GIPL-3-derived Galα1,6Galα1,3Galfβ glycotope for the serological diagnosis of American TL, particularly of the subclinical form.
Palabras clave en portugues
Leishmania braziliensisLeishmaniose tegumentar
Biomarcadores de diagnóstico e prognóstico
Neoglicoproteínas α-Gal
Anticorpos anti-α-Gal
Palabras clave en ingles
Leishmania braziliensisTegumentary leishmaniasis
Diagnostic and prognostic biomarkers
α-Gal neoglycoproteins
Anti-α-Gal antibodies
DeCS
Leishmania braziliensisTegumentary leishmaniasis
Biomarcadores
Diagnóstico
Prognóstico
Glicoproteínas
Anticorpos
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