Tuberculosis is a communicable disease caused by infection with M. tuberculosis (MTB) complex organisms (M. tuberculosis, M. bovis, M. africanum), which typically spread to new hosts via airborne droplet nuclei from patients with respiratory tuberculosis disease. A newly infected individual can become ill from tuberculosis within weeks to months, but most infected individuals remain well. Latent tuberculosis infection (LTBI), a
noncommunicable asymptomatic condition, persists in some who might develop tuberculosis disease months or years later. The main purpose of diagnosing LTBI is to consider medical treatment for preventing tuberculosis disease. Until recently, the tuberculin skin test (TST) was the only available method for diagnosing LTBI. Cutaneous sensitivity to tuberculin develops from 2 to 10 weeks after infection. However, some infected individuals, including those with a wide range of conditions hindering immune functions, but also others without these conditions, do not respond to tuberculin.
Conversely, some individuals who are unlikely to have M. tuberculosis infection exhibit sensitivity to tuberculin and have positive TST results after vaccination with Bacille Calmette-Guérin (BCG) or infection with mycobacteria other than M. tuberculosis complex, or undetermined other factors.
LTBI must be distinguished from tuberculosis disease, a reportable condition which usually involves the lungs and lower respiratory tract but may also affect other organ systems. Tuberculosis disease is diagnosed from historical, physical, radiological, histological, and mycobacteriological findings.
QFT-Plus is a test for cell-mediated immune (CMI) responses to peptide antigens that simulate mycobacterial proteins. These proteins, ESAT-6 and CFP-10, are absent from all BCG strains and from most nontuberculous mycobacteria with the exception of M. kansasii, M. szulgai, and M. marinum (1). Individuals infected with MTB-complex organisms usually have lymphocytes in their blood that recognize these and other mycobacterial antigens. This recognition process involves the generation and secretion of the cytokine IFN-γ. The detection and subsequent quantification of IFN-γ forms the basis of this test.
QuantiFERON-TB Gold Plus (QFT-Plus) ELISA Package Insert 02/2016 5 The antigens used in QFT-Plus are a peptide cocktail simulating the proteins ESAT-6 and CFP-10. Numerous studies have demonstrated that these peptide antigens stimulate IFN-γ responses in T cells from individuals infected with M. tuberculosis, but generally not from uninfected or BCG-vaccinated persons without disease or risk for LTBI).
However, medical treatments or conditions that impair immune functionality can potentially reduce IFN-γ responses. Patients with certain other mycobacterial infections might also be responsive to ESAT-6 and CFP-10, as the genes encoding these proteins are present in M. kansasii, M. szulgai, and M. marinum . QFT-Plus is both a test for LTBI and a helpful aid for diagnosing M. tuberculosis complex infection in sick patients. A positive result supports the diagnosis of tuberculosis disease, but infections by other mycobacteria (e.g., M. kansasii) could also lead to positive results. Other medical and diagnostic evaluations are necessary to confirm or exclude tuberculosis disease.
QFT-Plus has two distinct TB antigen tubes: TB Antigen Tube 1 (TB1) and TB Antigen Tube 2 (TB2). Both tubes contain peptide antigens from the MTB–complex–associated antigens, ESAT-6 and CFP-10. Whereas the TB1 tube contains peptides from ESAT-6 and CFP-10 that are designed to elicit CMI responses from CD4+ T-helper lymphocytes, the TB2 tube contains an additional set of peptides targeted to the induction of CMI responses from CD8+ cytotoxic T lymphocytes. In the natural history of MTB infection, CD4+ T cells play a critical role in immunological control through their secretion of the cytokine IFN-γ. Evidence now supports a role for CD8+ T cells participating in the host defense to MTB by producing IFN-γ and other soluble factors, which activate
macrophages to suppress growth of MTB, kill infected cells, or directly lyse intracellular MTB. MTB-specific CD8+ cells have been detected in subjects with LTBI and with active TB disease where IFN-γ producing CD8+ cells may be frequently found. Moreover, ESAT-6 and CFP-10 specific CD8+ T lymphocytes are described as
being more frequently detected in subjects with active TB disease versus LTBI, and may be associated with a recent MTB exposure. In addition, MTB-specific CD8+ T cells producing IFN-γ have also been detected in active TB subjects with HIV co-infection and in young children with TB disease.
Manufacturer’s Reagent package insert, QuantiFERON-TB Gold Plus (QFT-Plus) ELISA Package Insert, 02/2016.