Diagnostic accuracy of combinations of serological biomarkers for identifying clinical tuberculosis

  • Zaida Araujo Instituto de Biomedicina “Dr. Jacinto Convit”, Universidad Central de Venezuela, Caracas, Venezuela
  • Noe Macias-Segura Instituto Mexicano del Seguro Social, Zacatecas, México
  • Juan Ernesto Lopez-Ramos Instituto Mexicano del Seguro Social, Zacatecas, México
  • Jacobus Henry de Waard Instituto de Biomedicina “Dr. Jacinto Convit”, Universidad Central de Venezuela, Caracas, Venezuela
  • Magnolia Vanegas Fundación Instituto de Inmunología de Colombia, Bogotá, Colombia
  • Manuel Alfonso Patarroyo Fundación Instituto de Inmunología de Colombia, Bogotá, Colombia
  • Antonio Salgado Instituto de Biomedicina “Dr. Jacinto Convit”, Caracas, Venezuela
  • Jose Antonio Enciso-Moreno Instituto Mexicano del Seguro Social, Zacatecas, México
Keywords: Serological biomarker, synthetic peptide, IgG reactivity, TB

Abstract

Introduction: Confirmation of tuberculosis (TB) cases in endemic TB settings is a challenge; obtaining fast and cheap, though accurate, diagnostic tools such as biomarkers is thus urgently needed to enable the early detection of TB. This paper evaluates the diagnostic accuracy of combinations of host serological biomarkers for identifying TB.

Methodology: Enzyme-linked immunosorbent assays (ELISA) were used on 70 Venezuelan Creole individuals for evaluating host biomarkers (i.e. CXCL9, sCD14, MMP9 and uPAR proteins) and anti-synthetic peptides covering certain Mycobacterium tuberculosis (Mtb) ESAT-6 (P-12033, P-12034 and P-12037) and Ag85A (P-29878) antigen sequences. The target population consisted of adults having active TB (ATB, n = 28), the tuberculin skin test positive (TST+) or individuals with latent TB infection (LTB, n = 28) and TST- or control subjects (CTRL, n = 14).

Results: Receiver operator curve (ROC) analysis revealed good biosignature discriminative ability for 5 serological biomarkers; the accuracy of 3 combinations had a good discriminative ability for diagnosing TB. Anti-P-12034/uPAR detected TB with 96.7% sensitivity and 86.0% specificity, followed by anti-P-12033/uPAR having 96.7% sensitivity and 81.4% specificity. Anti-P-29878/MMP9 had the highest sensitivity (100%), but low specificity (52.17%). Biomarker combinations did not prove efficacious for identifying incipient subclinical TST+TB subjects at high-risk for TB.

Conclusions: The anti-P-12034/uPAR combination could be useful for identifying clinical TB patients. Such an approach holds promise for further validation.

Author Biographies

Zaida Araujo, Instituto de Biomedicina “Dr. Jacinto Convit”, Universidad Central de Venezuela, Caracas, Venezuela

Laboratorio de Inmunología de Enfermedades Infecciosas

Noe Macias-Segura, Instituto Mexicano del Seguro Social, Zacatecas, México

Unidad de Investigación Biomédica de Zacatecas

Juan Ernesto Lopez-Ramos, Instituto Mexicano del Seguro Social, Zacatecas, México

Unidad de Investigación Biomédica de Zacatecas

Jacobus Henry de Waard, Instituto de Biomedicina “Dr. Jacinto Convit”, Universidad Central de Venezuela, Caracas, Venezuela

Laboratorio de Tuberculosis

Magnolia Vanegas, Fundación Instituto de Inmunología de Colombia, Bogotá, Colombia

Departamento de Biología Molecular

Manuel Alfonso Patarroyo, Fundación Instituto de Inmunología de Colombia, Bogotá, Colombia

Departamento de Biología Molecular

Antonio Salgado, Instituto de Biomedicina “Dr. Jacinto Convit”, Caracas, Venezuela

Sección de Informática

Jose Antonio Enciso-Moreno, Instituto Mexicano del Seguro Social, Zacatecas, México

Unidad de Investigación Biomédica de Zacatecas

Published
2018-06-30
How to Cite
1.
Araujo Z, Macias-Segura N, Lopez-Ramos J, de Waard J, Vanegas M, Patarroyo M, Salgado A, Enciso-Moreno J (2018) Diagnostic accuracy of combinations of serological biomarkers for identifying clinical tuberculosis. J Infect Dev Ctries 12:429-441. doi: https://doi.org/10.3855/jidc.9554
Section
Original Articles