Novel M tuberculosis antigen-specific T-cells are early markers of infection and disease progression

PLoS One. 2011;6(12):e28754. doi: 10.1371/journal.pone.0028754. Epub 2011 Dec 28.

Abstract

Background: Mycobacterium tuberculosis Region-of-Difference-1 gene products present opportunities for specific diagnosis of M. tuberculosis infection, yet immune responses to only two gene-products, Early Secretory Antigenic Target-6 (ESAT-6) and Culture Filtrate Protein-10 (CFP-10), have been comprehensively investigated.

Methods: T-cell responses to Rv3873, Rv3878 and Rv3879c were quantified by IFN-γ-enzyme-linked-immunospot (ELISpot) in 846 children with recent household tuberculosis exposure and correlated with kinetics of tuberculin skin test (TST) and ESAT-6/CFP-10-ELISpot conversion over six months and clinical outcome over two years.

Results: Responses to Rv3873, Rv3878, and Rv3879c were present in 20-25% of contacts at enrolment. Rv3873 and Rv3879c responses were associated with and preceded TST conversion (P=0.02 and P=0.04 respectively), identifying these antigens as early targets of cell-mediated immunity following M. tuberculosis exposure. Responses to Rv3873 were additionally associated with subsequent ESAT-6/CFP-10-ELISpot conversion (P=0.04). Responses to Rv3873 and Rv3878 predicted progression to active disease (adjusted incidence rate ratio [95% CI] 3.06 [1.05,8.95; P=0.04], and 3.32 [1.14,9.71; P=0.03], respectively). Presence of a BCG-vaccination scar was associated with a 67% (P=0.03) relative risk reduction for progression to active tuberculosis.

Conclusions: These RD1-derived antigens are early targets of cellular immunity following tuberculosis exposure and T-cells specific for these antigens predict progression to active tuberculosis suggesting diagnostic and prognostic utility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunodominant Epitopes / immunology
  • Interferon-gamma / immunology
  • Mycobacterium tuberculosis / immunology*
  • T-Lymphocytes / immunology*
  • Tuberculin Test

Substances

  • Antigens, Bacterial
  • Immunodominant Epitopes
  • Interferon-gamma