Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens

Am J Respir Crit Care Med. 2004 Jul 1;170(1):59-64. doi: 10.1164/rccm.200402-179OC. Epub 2004 Apr 1.


The tuberculin skin test for immunologic diagnosis of Mycobacterium tuberculosis infection has many limitations, including being confounded by bacillus Calmette-Guérin (BCG) vaccination or exposure to nontuberculous mycobacteria. M. tuberculosis-specific antigens that are absent from BCG and most nontuberculous mycobacteria have been identified. We examined the use of two of these antigens, CFP-10 and ESAT-6, in a whole blood IFN-gamma assay as a diagnostic test for tuberculosis in BCG-vaccinated individuals. Because of the lack of an accurate standard with which to compare new tests for M. tuberculosis infection, specificity of the whole blood IFN-gamma assay was estimated on the basis of data from people with no identified risk for M. tuberculosis exposure (216 BCG-vaccinated Japanese adults) and sensitivity was estimated on the basis of data from 118 patients with culture-confirmed M. tuberculosis infection who had received less than 1 week of treatment. Using a combination of CFP-10 and ESAT-6 responses, the specificity of the test for the low-risk group was 98.1% and the sensitivity for patients with M. tuberculosis infection was 89.0%. The results demonstrate that the whole blood IFN-gamma assay using CFP-10 and ESAT-6 was highly specific and sensitive for M. tuberculosis infection and was unaffected by BCG vaccination status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Bacterial / immunology*
  • BCG Vaccine / immunology
  • Bacterial Proteins / immunology*
  • Cross Reactions
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes
  • Female
  • Humans
  • Immunoassay / methods*
  • Immunologic Memory
  • Interferon-gamma / metabolism
  • Male
  • Mycobacterium tuberculosis / immunology*
  • Sensitivity and Specificity
  • T-Lymphocytes / immunology
  • Tuberculin Test
  • Tuberculosis / diagnosis*
  • Vaccination


  • Antigens, Bacterial
  • BCG Vaccine
  • Bacterial Proteins
  • CFP-10 protein, Mycobacterium tuberculosis
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Epitopes
  • Interferon-gamma