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Open AccessArticle

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

1
Department of Bacteriology and Epidemiology, Wageningen Bioveterinary Research, Houtribweg 398221 RA Lelystad, The Netherlands
2
Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 73584 CL Utrecht, The Netherlands
3
Independent Researcher, 8212 AM Lelystad, The Netherlands
*
Author to whom correspondence should be addressed.
Vet. Sci. 2019, 6(4), 91; https://doi.org/10.3390/vetsci6040091
Received: 30 September 2019 / Revised: 4 November 2019 / Accepted: 8 November 2019 / Published: 13 November 2019
(This article belongs to the Special Issue Mycobacterial Diseases in Animals)
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. View Full-Text
Keywords: Mycobacterium avium subsp. paratuberculosis; Mycobacterium bovis; glycolipid; phosphatidylinositol mannosides; cattle; tuberculosis; paratuberculosis; diagnosis Mycobacterium avium subsp. paratuberculosis; Mycobacterium bovis; glycolipid; phosphatidylinositol mannosides; cattle; tuberculosis; paratuberculosis; diagnosis
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Koets, A.P.; van den Esker, M.H.; Riepema, K.; Bakker, D. The Role of Phosphatidylinositol Mannosides in the Serological Diagnosis of Mycobacterial Infections. Vet. Sci. 2019, 6, 91.

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