Gamma Interferon Assays Used in the Diagnosis of Tuberculosis

Abstract

Tuberculosis (TB) is an ancient disease that has infected humans for thousands of years. However, despite diagnostic tests that detect the disease and effective therapy, there are still millions of people worldwide who are infected with TB. The first TB test used to detect infected patients was a skin test that identifies individuals actively infected with TB. This test used a mix of proteins from culture filtrates of the bacteria Mycobacterium tuberculosis. Recently, two new diagnostic tests have been introduced; these two new tests can detect TB infection in patients by challenging peripheral blood cells with specific TB proteins. These assays measure the cellular immune response to these proteins. This minireview evaluates the new assays and compares them to the use of the TB skin test. The use of these new assays may have some advantages in detecting individuals with active tuberculosis. However, there is still a role for the use of the skin test, especially in young patients.

Prevalencia de infección tuberculosa latente en trabajadores de salud de establecimientos del primer nivel de atención. Lima, Perú

“…En la actualidad existen otros métodos diagnósticos basados en la cuantificación in vitro de la respuesta inmune celular, los llamados ensayos de liberación de interferón gamma (IGRA, por su traducción del inglés interferon gamma release assays) (13,14) .…”

Comparative Evaluation of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus in Diagnosis of Latent Tuberculosis Infection in Immunocompromised Patients

“…IGRAs do not yield false-positive results in M. bovis bacillus Calmette-Guérin (BCG)-vaccinated individuals due to the absence of cross-reactivity with the BCG strain and do not require a second visit, as is needed for TST. Moreover, the IGRA is more objective in terms of the procedure and interpretation of the results (12). However, there are limitations, such as an inability to distinguish between active tuberculosis and LTBI (13,14), a poor correlation between LTBI detection and the risk of developing active disease (13,(15)(16)(17), and a relatively poor sensitivity of LTBI detection in children and immunocompromised individuals (13,(18)(19)(20)(21).…”

Two-Year Follow-up Study of Mycobacterium tuberculosis Antigen-Driven IFN-γ Responses and Macrophage sCD14 Levels After Tuberculosis Contact

“…Currently, the diagnosis of LTBI relies on specific M.tb antigen-driven IFN-c responses measured in IGRA assays and flow cytometry assays of M.tb antigen driven effector T cell responses [5,15]. In our longitudinal study, we assessed IFN-c responses to specific M.tb antigens (ESAT-6, CFP-10, TB7.7) using QFT, in 60 healthy Polish volunteers with recent domestic or long lasting occupational TB contact and those not exposed to infectious TB.…”

“…However, the identification of latently-infected individuals with the highest risk of progression to active disease is still problematic. The standard technique for diagnosing LTBI is the tuberculin skin test (TST), which measures delayed-type hypersensitivity to a mycobacterial purified protein derivative (PPD), which is present in M.tb, BCG vaccine strains and many non-tuberculous mycobacteria [5]. Therefore, TST positivity can occur as a result of prior BCG immunization or infection with environmental mycobacteria.…”

“…Therefore, TST positivity can occur as a result of prior BCG immunization or infection with environmental mycobacteria. More specific detection of LTBI has become possible with the development of the in vitro T cell-based interferon-gamma (IFN-c) release assays (IGRAs) based on the principle that lymphocytes of individuals infected with M.tb produce IFN-c in response to pathogen-specific antigens, early secretory antigenic target-6 (ESAT-6), culture filtrate protein 10 (CFP-10), and/or TB7.7 [4][5][6][7]. These antigens are absent from the M. bovis BCG strains and from the majority of nontuberculous mycobacteria with the exception of M. kansasii, M. szulgai, and M. marinum [8].…”