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The Role of Phosphatidylinositol Mannosides in the Serological Diagnosis of Mycobacterial Infections

Accurate diagnosis of mycobacterial infections, such as bovine tuberculosis and paratuberculosis, remains challenging. Available direct diagnostic tests aimed at detecting the pathogen are highly specific but lack sensitivity, depending on the stage of infection and the prevalence of infection in a...

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Autores principales: Koets, Ad P., van den Esker, Marielle H., Riepema, Karel, Bakker, Douwe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958488/
https://www.ncbi.nlm.nih.gov/pubmed/31766256
http://dx.doi.org/10.3390/vetsci6040091
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author Koets, Ad P.
van den Esker, Marielle H.
Riepema, Karel
Bakker, Douwe
author_facet Koets, Ad P.
van den Esker, Marielle H.
Riepema, Karel
Bakker, Douwe
author_sort Koets, Ad P.
collection PubMed
description Accurate diagnosis of mycobacterial infections, such as bovine tuberculosis and paratuberculosis, remains challenging. Available direct diagnostic tests aimed at detecting the pathogen are highly specific but lack sensitivity, depending on the stage of infection and the prevalence of infection in a population. The sensitivity of indirect diagnostic assays that measure the host immune response to infection is similarly affected by disease characteristics. The choice of antigen used to detect a host response to infection has a critical impact on test sensitivity and specificity. Many indirect tests rely on crude antigen preparations and cell-free extracts, of which the production is poorly standardized. Moreover, these preparations contain ample uncharacterized cross-reactive compounds. To enhance serological test specificity, existing assays depend on the pre-treatment of samples and a relatively high cut-off value, that in turn influences test sensitivity. Research therefore focuses on the identification of more specific, defined antigens to improve diagnostics. In the current study, we extracted phosphatidylinositol mannosides (PIMs) and investigated their potential use in antibody-based tests. Our results demonstrate that specific IgG class antibodies are generated against PIMs in cows, but this is unrelated to tuberculosis or paratuberculosis infection status, making these antigens unsuitable for diagnostic applications. In addition, we demonstrate that PIMs are widely present in crude antigen preparations and in serum pre-absorption buffer. Our results indicate that PIMs are cross-reactive compounds with immunodominant B cell epitopes that could impair serological test specificity.
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spelling pubmed-69584882020-01-23 The Role of Phosphatidylinositol Mannosides in the Serological Diagnosis of Mycobacterial Infections Koets, Ad P. van den Esker, Marielle H. Riepema, Karel Bakker, Douwe Vet Sci Article Accurate diagnosis of mycobacterial infections, such as bovine tuberculosis and paratuberculosis, remains challenging. Available direct diagnostic tests aimed at detecting the pathogen are highly specific but lack sensitivity, depending on the stage of infection and the prevalence of infection in a population. The sensitivity of indirect diagnostic assays that measure the host immune response to infection is similarly affected by disease characteristics. The choice of antigen used to detect a host response to infection has a critical impact on test sensitivity and specificity. Many indirect tests rely on crude antigen preparations and cell-free extracts, of which the production is poorly standardized. Moreover, these preparations contain ample uncharacterized cross-reactive compounds. To enhance serological test specificity, existing assays depend on the pre-treatment of samples and a relatively high cut-off value, that in turn influences test sensitivity. Research therefore focuses on the identification of more specific, defined antigens to improve diagnostics. In the current study, we extracted phosphatidylinositol mannosides (PIMs) and investigated their potential use in antibody-based tests. Our results demonstrate that specific IgG class antibodies are generated against PIMs in cows, but this is unrelated to tuberculosis or paratuberculosis infection status, making these antigens unsuitable for diagnostic applications. In addition, we demonstrate that PIMs are widely present in crude antigen preparations and in serum pre-absorption buffer. Our results indicate that PIMs are cross-reactive compounds with immunodominant B cell epitopes that could impair serological test specificity. MDPI 2019-11-13 /pmc/articles/PMC6958488/ /pubmed/31766256 http://dx.doi.org/10.3390/vetsci6040091 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Koets, Ad P.
van den Esker, Marielle H.
Riepema, Karel
Bakker, Douwe
The Role of Phosphatidylinositol Mannosides in the Serological Diagnosis of Mycobacterial Infections
title The Role of Phosphatidylinositol Mannosides in the Serological Diagnosis of Mycobacterial Infections
title_full The Role of Phosphatidylinositol Mannosides in the Serological Diagnosis of Mycobacterial Infections
title_fullStr The Role of Phosphatidylinositol Mannosides in the Serological Diagnosis of Mycobacterial Infections
title_full_unstemmed The Role of Phosphatidylinositol Mannosides in the Serological Diagnosis of Mycobacterial Infections
title_short The Role of Phosphatidylinositol Mannosides in the Serological Diagnosis of Mycobacterial Infections
title_sort role of phosphatidylinositol mannosides in the serological diagnosis of mycobacterial infections
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958488/
https://www.ncbi.nlm.nih.gov/pubmed/31766256
http://dx.doi.org/10.3390/vetsci6040091
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