Developing a diagnostic method for latent tuberculosis infection using circulating miRNA

Abstract

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.