74 Beyond the Binary: Understanding the Factors Behind Indeterminate Results on the QuantiFERON-TB Gold Plus Assay

Abstract QuantiFERON(R) TB Gold is a test used to diagnose tuberculosis (TB) infection by measuring interferon-gamma release. Test results can be positive, negative, or indeterminate. The American College of Rheumatology recommends interferon-gamma release assays as the initial test for rheumatoid arthritis patients beginning biological agents. Recently, our laboratory noted an increase in TB tests due to the US Preventive Services Task Force’s recommendation for TB testing in high-risk populations for latent TB infection screening. We also observed a rise in indeterminate results, prompting inquiries from providers. In this study, we conducted a retrospective data analysis to investigate indeterminate TB results and identify potential factors contributing to these outcomes. ​​​​​​​QuantiFERON(R) TB Gold is a test that helps diagnose tuberculosis (TB) infection by measuring interferon-gamma release (IGR). The test results can be either positive, negative, or indeterminate. The American College of Rheumatology recommends IGR assays as the first test for rheumatoid arthritis patients starting biological agents. The laboratory recently noticed an increase in TB tests conducted due to the US Preventive Services Task Force’s recommendation of TB testing for latent TB infection screening in high-risk populations. We also noticed an increase in indeterminate results in our laboratory, which resulted in inquiries from the caregivers. In this study, we analyzed retrospective data to identify potential factors contributing to indeterminate results. Methods The QuantiFERON-TB Gold Plus IFN-γ assay in our laboratory is performed on the Agility (Dynex Technologies, Chantilly, VA) automated ELISA processor, which performs all necessary calculations to determine the nil, mitogen minus nil, and TB antigen minus nil IFN-γ values for the QFT-GIT assay. We conducted a retrospective analysis of four years’ worth of data, examining the percentage of indeterminate results and considering race, ethnicity, and reason for the outcome. Results Over 4 years, 17,743 individuals underwent testing for tuberculosis (TB). Out of all the cases, 128 individuals had indeterminate results, which accounts for approximately 0.7% of the total cases. In the 128 cases examined, 53% of patients were female and 47% were male. The racial distribution was 41% African American and 59% non-African American. The indeterminate results were mainly due to various factors, such as 20% of the patients being immigrants, 59% being immunocompromised, 18% due to pre-analytical issues, and only 2% having TB-associated factors. Conclusion Upon analyzing our data, we have determined that various factors can lead to indeterminate results. These factors include a compromised immune system due to immunosuppressive therapy, the Bacille Calmette-Guérin vaccine in immigrants, and pre-analytical issues such as processing delays. The majority of individuals with indeterminate results were found to be immunocompromised.