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Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]

dc.creatorRubio-Carrasquilla M.
dc.creatorOchoa R.
dc.creatorSanta C.
dc.creatorGuimarães A.J.
dc.creatorCano L.E.
dc.creatorMoreno E.
dc.date2019
dc.date.accessioned2020-04-29T14:54:07Z
dc.date.available2020-04-29T14:54:07Z
dc.identifier.issn11301406
dc.identifier.urihttp://hdl.handle.net/11407/5812
dc.descriptionBackground: In a previous work we showed the feasibility of an interferon gamma release assay (IGRA) for detecting latent infection by Histoplasma capsulatum. While in that proof-of-concept study we used crude fungal extracts as antigens, the newest IGRAs developed for other infections are based on molecularly defined antigens, mostly on mixtures of immunogenic peptides. Aims: To identify proteins in H. capsulatum that might serve as molecularly defined antigens for an IGRA test. Methods: We surveyed the literature looking for known H. capsulatum-immunogenic proteins and assayed two of them as antigens in an IGRA test, in a study that involved 80 volunteers. Furthermore, we used several bioinformatics tools to identify specific H. capsulatum proteins and to analyze possible strategies for the design of H. capsulatum-specific immunogenic peptides. Results: Seven H. capsulatum-immunogenic proteins were retrieved from the literature. IGRA tests using either the heat shock protein 60 or the M antigen showed high sensitivities but low specificities, most likely due to the high sequence similarity with the corresponding orthologs in other pathogenic microorganisms. We identified around 2000 H. capsulatum-specific proteins, most of which remain unannotated. Class II T-cell epitope predictions for a small number of these proteins showed a great variability among different alleles, prompting for a brute force approach for peptide design. Conclusions: The H. capsulatum genome encodes a large number of distinctive proteins, which represent a valuable source of potential specific antigens for an IGRA test. Among them, the Cfp4 protein stands out as a very attractive candidate. © 2019 Asociación Española de Micología
dc.language.isoeng
dc.language.isospa
dc.publisherAsociacion Espanola de Micologia
dc.relation.isversionofhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85075592310&doi=10.1016%2fj.riam.2019.06.002&partnerID=40&md5=af0fd57be13f4e5f724549fc8c674fa4
dc.sourceRevista Iberoamericana de Micologia
dc.subjectHistoplasma capsulatum
dc.subjectIGRA
dc.subjectImmunogenic proteins
dc.subjectMolecularly defined antigens
dc.subjectT-cell epitopes
dc.subjectalcohol dehydrogenase
dc.subjectankyrin repeat protein
dc.subjectbeta lactamase
dc.subjectchaperonin 60
dc.subjectDUF636 domain containing protein
dc.subjectepitope
dc.subjectfungus antigen
dc.subjectM antigen
dc.subjectproteoglycan
dc.subjectsynthetic peptide
dc.subjectunclassified drug
dc.subjectallele
dc.subjectamino acid sequence
dc.subjectantigen detection
dc.subjectantigenic variation
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectHistoplasma capsulatum
dc.subjecthuman
dc.subjectimmunogenicity
dc.subjectinterferon gamma release assay
dc.subjectnonhuman
dc.subjectorthology
dc.subjectpathogenicity
dc.subjectprotein analysis
dc.subjectsensitivity and specificity
dc.subjectvolunteer
dc.titleIdentifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]
dc.typeArticleeng
dc.rights.accessrightsinfo:eu-repo/semantics/restrictedAccess
dc.publisher.programFacultad de Ciencias Básicas
dc.identifier.doi10.1016/j.riam.2019.06.002
dc.relation.citationvolume36
dc.relation.citationissue4
dc.relation.citationstartpage186
dc.relation.citationendpage191
dc.publisher.facultyFacultad de Ciencias Básicas
dc.affiliationRubio-Carrasquilla, M., Grupo de Micología Médica y Experimental, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia, Instituto de Biología, Universidad de Antioquia, Medellín, Colombia; Ochoa, R., Programa de Estudio y Control de Enfermedades Tropicales PECET, Universidad de Antioquia, Medellín, Colombia; Santa, C., Universidad Nacional de Colombia, Sede Medellín, Medellín, Colombia; Guimarães, A.J., Depto de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói, RJ, Brazil; Cano, L.E., Grupo de Micología Médica y Experimental, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia, Escuela de Microbiología, Universidad de Antioquia, Medellín, Colombia; Moreno, E., Facultad de Ciencias Básicas, Universidad de Medellín, Medellín, Colombia
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dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.type.driverinfo:eu-repo/semantics/article


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