Further interpretation of IGRA test
Higher levels of interferon-gamma (IFN-g) have been associated with an increased risk of progression to active TB (Ledesma et al, 2021); but research is ongoing to determine if and how the IGRA test can predict the presence or progression to active TB disease.
Limitations
- Collection (wrong tube type), processing technique (eg., failure to mix, incorrect incubation), and analytic errors (eg., pipetting, reagent prep, and storage) may cause false negative or false-positive results.
- High cost compared to TST.
- ESAT-6 and CFP-10 peptides are absent from most known nontuberculous mycobacteria, but false-positives (interference) may occur in cases where the individual is infected with M. kansasii, M. szulgai, or M. marinum.
- Immunosuppressed or immunocompromised populations may lead to false-negative results. (The immune system is suppressed, or the immune reaction has not had sufficient time to mount prior to testing.)
- Administration of BCG vaccine may cause a false positive result (Pai et al, 2014); however, newer generations of IGRA tests are mostly unaffected by prior BCG vaccination. IGRA is recommended in individuals who have received prior BCG vaccination.
- Additional consideration: Immune mechanisms of some high-risk exposures may lead to early clearance of MTB prior to the development of an immune response (Meermeier and Lewinsohn, 2018), leading to a negative IGRA when a positive IGRA was expected. (An immune response was not mounted.)
