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Detection of the tuberculosis antigenic marker mannose-capped lipoarabinomannan in pretreated serum by surface-enhanced Raman scattering.
Crawford, Alexis C; Laurentius, Lars B; Mulvihill, Timothy S; Granger, Jennifer H; Spencer, John S; Chatterjee, Delphi; Hanson, Kimberly E; Porter, Marc D.
Afiliação
  • Crawford AC; Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA and Nano Institute of Utah, University of Utah, Salt Lake City, UT 84112, USA. marc.porter@utah.edu.
  • Laurentius LB; Nano Institute of Utah, University of Utah, Salt Lake City, UT 84112, USA. marc.porter@utah.edu.
  • Mulvihill TS; Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
  • Granger JH; Nano Institute of Utah, University of Utah, Salt Lake City, UT 84112, USA. marc.porter@utah.edu.
  • Spencer JS; Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
  • Chatterjee D; Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
  • Hanson KE; Departments of Internal Medicine and Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
  • Porter MD; Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA and Nano Institute of Utah, University of Utah, Salt Lake City, UT 84112, USA. marc.porter@utah.edu and Department of Chemical Engineering, University of Utah, Salt Lake City, UT 84112, USA and Department of Bioengineering, U
Analyst ; 142(1): 186-196, 2016 12 19.
Article em En | MEDLINE | ID: mdl-27924983
The ability to detect tuberculosis (TB) continues to be a global health care priority. This paper describes the development and preliminary assessment of the clinical accuracy of a heterogeneous immunoassay that integrates a serum pretreatment process with readout by surface-enhanced Raman scattering (SERS) for the low-level detection of mannose-capped lipoarabinomannan (ManLAM). ManLAM is a major virulence factor in the infectious pathology of Mycobacterium tuberculosis (Mtb) that has been found in the serum and other body fluids of infected patients. The effectiveness of ManLAM as a TB diagnostic marker, however, remains unproven for reasons not yet well understood. As reported herein, we have found that (1) ManLAM complexes with proteins and possibly other components in serum; (2) these complexes have a strongly detrimental impact on the ability to detect ManLAM using an immunoassay; (3) a simple pretreatment step can disrupt this complexation; and (4) disruption by pretreatment improves detection by 250×. We also describe the results from a preliminary assessment on the utility of serum pretreatment by running immunoassays on archived specimens from 24 TB-positive patients and 10 healthy controls. ManLAM was measurable in 21 of the 24 TB-positive specimens, but not in any of the 10 control specimens. These findings, albeit for a very small specimen set, translate to a clinical sensitivity of 87.5% and a clinical specificity of 100%. Together, these results both provide much needed evidence for the clinical utility of ManLAM as a TB marker, and demonstrate the potential utility of our overall approach to serve as a new strategy for the development of diagnostic tests for this disease.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Análise Espectral Raman / Lipopolissacarídeos / Manose / Mycobacterium tuberculosis / Antígenos de Bactérias Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Análise Espectral Raman / Lipopolissacarídeos / Manose / Mycobacterium tuberculosis / Antígenos de Bactérias Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article