Developing a diagnostic method for latent tuberculosis infection using circulating miRNA
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(2020) 5:25
RESEARCH
Translational Medicine Communications
Open Access
Developing a diagnostic method for latent tuberculosis infection using circulating miRNA Shoji Hashimoto1, Hong Zhao2, Michiyo Hayakawa3, Koichi Nakajima2, Y-h Taguchi4 and Yoshiki Murakami5*
Abstract Background: Mycobacterium tuberculosis is known to cause latent tuberculosis infection (LTBI) in 25–50% of the cases, of whom 10–20% develop active tuberculosis (TB). Notably, no marker currently exists for judging the therapeutic effect of TB; it is currently judged by chest X-ray and clinical symptoms. We attempted to establish a marker for distinguishing LTBI from active TB and to identify the probability of recurrence after TB treatment, using information on circulating miRNA expression. Methods: In total, 32 patients were enrolled in this study: 16 with an onset or recurrence of active TB, and 16 with LTBI showing positive interferon-gamma release assays (IGRA) test and chest X-ray. Total RNA from serum in an exosome-rich fraction was first extracted, followed by miRNA expression analysis using a next-generation sequencer, then, this data were analyzed using miRDeep2. Results: Using the expression information of eight miRNAs, LTBI and TB could be diagnosed with an accuracy of 71.8% (odds ratio: 6.16, p value = 3.20e-02). Conclusions: A novel method for efficiently differentiating between LTBI and active TB was established. This method appears to be promising for evaluating the therapeutic effect of TB, as it can be performed in a minimally invasive manner. Keywords: LTBI, TB, miRNA, Next-generation sequencing
Background Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that affects the lungs. It is estimated that nearly 25% of the world’s population is affected by TB [1]. The reason behind the uncontrollability of TB infection is not only poverty and coinfection with human immunodeficiency virus but also the lack of adequate information on the transmission and pathogenesis of this disease. Notably, nearly 5–15% of the people infected with TB develop overt infection, whereas most patients have latent tuberculosis infection (LTBI). However, patients with overt infection are at a risk of * Correspondence: [email protected] 5 Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan Full list of author information is available at the end of the article
reactivation after completing their treatment [2]. Therefore, in TB treatment, it is important to diagnose LTBI and prevent the development of TB from LTBI. Once infected with TB, most people remain asymptomatic and noncontagious. However, 5–15% of cases with LTBI may progress to active TB during their lifetime and become infectious [3]. The risk of progression becomes even higher in younger children [4] and immunocompromised or immunosuppressed patients [5, 6]. Though for a long time tuberculin skin test (TST) had been used for the diagnosis of TB, now blood-based interferon-gamma release assays
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