Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1783487425205501952 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6958488 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT koetsadp theroleofphosphatidylinositolmannosidesintheserologicaldiagnosisofmycobacterialinfections AT vandeneskermarielleh theroleofphosphatidylinositolmannosidesintheserologicaldiagnosisofmycobacterialinfections AT riepemakarel theroleofphosphatidylinositolmannosidesintheserologicaldiagnosisofmycobacterialinfections AT bakkerdouwe theroleofphosphatidylinositolmannosidesintheserologicaldiagnosisofmycobacterialinfections AT koetsadp roleofphosphatidylinositolmannosidesintheserologicaldiagnosisofmycobacterialinfections AT vandeneskermarielleh roleofphosphatidylinositolmannosidesintheserologicaldiagnosisofmycobacterialinfections AT riepemakarel roleofphosphatidylinositolmannosidesintheserologicaldiagnosisofmycobacterialinfections AT bakkerdouwe roleofphosphatidylinositolmannosidesintheserologicaldiagnosisofmycobacterialinfections |