Abstract
The QuantiFERON®-TB Gold In-Tube test (QFT), an interferon-γ release assay, is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in distinguishing active tuberculosis from latent infection is a major concern. There is thus a need for an easy and accurate tool for achieving that goal in daily clinical settings. This study aimed to identify candidate cytokines for specifically differentiating active tuberculosis from latent infection. Our study population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent tuberculosis infection) patients and 10 healthy control subjects. We assayed for 27 cytokines in QFT supernatants of both specific antigen-stimulated blood samples (TBAg) and negative-control samples (Nil). We analyzed their specificities and sensitivities by creating receiver operating characteristic (ROC) curves and measuring the area under those curves (AUCs). In TBAg–Nil supernatants, IL-10, IFN-γ, MCP-1 and IL-1RA showed high AUCs of 0.8120, 0.7842, 0.7419 and 0.7375, respectively. Compared with each cytokine alone, combined assay for these top four cytokines showed positive rates in diagnosing active TB, and GDA analysis revealed that MCP-1 and IL-5 are potent in distinguishing active TB from LTBI, with Wilk’s lambda = 0.718 (p < 0.001). Furthermore, utilizing the unique characteristic of IL-2 that its TBAg–Nil supernatant levels are higher in LTBI compared to active TB, the difference between IFN-γ and IL-2 showed a large AUC of 0.8910. In summary, besides IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatants may be useful for distinguishing active TB from LTBI. Those cytokines may also help us understand the difference in pathogenesis between active TB and LTBI.
Highlights
Tuberculosis is still among the most dangerous communicable infectious diseases in the world
We identified IL-2, IL-5, IL-10, IL-1RA and MCP-1 as new candidates to be measured in QuantiFERON1-TB Gold In-Tube test (QFT) supernatants for better differentiation of active TB from LTBI
We found that several cytokines in negative-control samples (Nil) as well as tuberculosis-specific antigens (TBAg)-stimulated QFT supernatants were useful in differentiating active TB from LTBI
Summary
Tuberculosis is still among the most dangerous communicable infectious diseases in the world. Despite Japan’s high level of social health care, active tuberculosis is still seen Another problem is that new cases are often (multi-)drug-resistant. Other complicating factors include increased prescription of immune-suppressive medications for specific diseases such as cancer and rheumatic diseases, increased numbers of immigrants and travelers from developing countries with a higher incidence of active TB, and increased prevalence of acquired immune disorders such as HIV infection. These multiple factors make diagnosis and management of M. tuberculosis infection even more complex and challenging than before [2, 3]. There is a need for more accurate, faster and easier diagnosis of M. tuberculosis, which would permit early treatment
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