From the Guidelines
NTM species that can cause false-positive results on Interferon-Gamma Release Assays (IGRAs) include Mycobacterium kansasii, Mycobacterium szulgai, and Mycobacterium marinum, as they contain antigens that cross-react with the ESAT-6 and CFP-10 antigens used in IGRA tests, as stated in the 2010 guidelines 1. These species can lead to false-positive IGRA results due to the presence of ESAT-6 and CFP-10 antigens, which are also found in Mycobacterium tuberculosis.
- The cross-reactivity occurs because these NTM species possess genetic regions similar to the RD1 region of Mycobacterium tuberculosis that encodes these specific antigens.
- When a patient has been exposed to or infected with these NTM species, their T-cells may recognize and respond to the IGRA test antigens, producing interferon-gamma and yielding a positive result despite the absence of true tuberculosis infection, as noted in the guidelines for using QuantiFERON-TB Gold test (QFT-G) 1.
- This is particularly problematic in regions with high NTM prevalence or in immunocompromised patients who are more susceptible to NTM infections.
- Clinicians should consider this possibility when interpreting positive IGRA results, especially in patients with low tuberculosis risk factors but potential NTM exposure, and use the most recent and highest quality studies, such as the 2010 guidelines 1, to guide their decision-making.
From the Research
Species of NTM that Cause False Positive on IGRA
- Mycobacterium kansasii, Mycobacterium marinum, and Mycobacterium szulgai may induce positive IGRAs due to RD1 homology with Mycobacterium tuberculosis 2, 3
- Mycobacterium gordonae, Mycobacterium flavescens are also mentioned as potential causes of false positive IGRA results 3
- The QuantiFERON-TB-Gold Test (QFT) was positive in 8% of patients with definite NTM disease, with the lowest positivity rate among patients infected with NTM without the RD1 region 4
Performance of IGRA in NTM Infections
- The QFT holds potential to discriminate between NTM and MTB infections, but may not be able to distinguish between active TB and MAC disease or latent TB infection in a TB-endemic area 4, 5
- The performance of IGRA may vary depending on the specific NTM species and the presence of the RD1 region 2, 4
Specific NTM Species and IGRA Results
- Mycobacterium kansasii: associated with positive IGRA results in 22% of patients 2
- Mycobacterium avium: QFT-G and QFT tests were positive in 34.3% and 35.3% of patients with MAC lung disease, respectively 5
- Mycobacterium intracellulare, Mycobacterium abscessus, and other NTM species: correct detection rates using nucleotide MALDI-TOF-MS were high, but IGRA results were not specifically reported 6