Original articleIdentifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assayIdentificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum
Section snippets
Identification of H. capsulatum antigens
Two alternative strategies were explored in parallel to identify possible molecularly defined antigens that might be used in a H. capsulatum-specific IGRA test: (i) Searching for H. capsulatum proteins that have been previously characterized as immunogenic molecules; and (ii) Identification of specific H. capsulatum proteins, that is, proteins that do not have close orthologs in other related fungi. In both cases, the identified proteins might be used in the form of complete proteins or as
Immunogenic H. capsulatum proteins known from the literature
Table 1 lists seven proteins which have been evaluated before in multiple studies aiming to establish their role in the pathogenesis and immune response against H. capsulatum. Some of these proteins are part of the membrane and cell wall of the yeast phase, while others are secreted to the extracellular environment. Because of their proven immunogenicity, these proteins represent possible molecular antigens for a H. capsulatum-specific IGRA test.
IGRA tests using HSP60 or M antigen showed lack of specificity
We evaluated two of the H. capsulatum immunogenic
Conclusions
The development of an IGRA test for detecting latent infections by H. capsulatum should evolve toward the use of molecularly defined antigens, preferably immunogenic peptides. The use of known immunogenic H. capsulatum proteins having a high sequence similarity with their orthologs in other pathogenic microorganisms may result in a low test specificity, as demonstrated here for M and HSP60 antigens. Our bioinformatics analyses show that the H. capsulatum genome encodes a large number of
Funding
This work was supported by COLCIENCIAS (grant 221356933526) and the University of Antioquia (CODI-UdeA grant CIEMB-098-13).
Conflict of interest
The authors declare that they have no conflict of interest.
References (29)
- et al.
Predicting subcellular localization of proteins based on their N-terminal amino acid sequence
J Mol Biol
(2000) - et al.
Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes
J Mol Biol
(2001) - et al.
Endemic mycoses in solid organ transplant recipients
Infect Dis Clin N Am
(2018) - et al.
Development of a whole blood assay to measure T cell responses to leprosy: a new tool for immuno-epidemiological field studies of leprosy immunity
J Immunol Methods
(1994) - et al.
Mapping immune reactivity toward Rv2653 and Rv2654: two novel low-molecular-mass antigens found specifically in the Mycobacterium tuberculosis complex
J Infect Dis
(2004) - et al.
Histoplasmosis in HIV-infected patients: a review of new developments and remaining gaps
Curr Trop Med Rep
(2014) - et al.
Vesicular transport in Histoplasma capsulatum: an effective mechanism for trans-cell wall transfer of proteins and lipids in ascomycetes
Cell Microbiol
(2008) - et al.
Intrapulmonary response to Histoplasma capsulatum in gamma interferon knockout mice
Infect Immun
(1997) - et al.
First independent evaluation of QuantiFERON-TB Plus performance
Eur Respir J
(2016) - et al.
Feature-based prediction of non-classical and leaderless protein secretion
Protein Eng Des Sel
(2004)
Diagnosis of congenital toxoplasmosis by using a whole-blood gamma interferon release assay
J Clin Microbiol
Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic hepatitis B patients
J Transl Med
Histoplasma capsulatum (histoplasmosis)
Mandell, Douglas, and Bennett's principles and practice of infectious diseases
Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite
PLoS ONE
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