Circulating Serum RNA Transcripts Differ Between Latent and Active Tuberculosis

Researchers have identified specific host-derived circulating serum RNA transcripts that show significant differences in abundance between individuals with latent tuberculosis infection and those with active disease. According to findings published in BMC Infectious Diseases, relative expression levels of CXCL10, L6, and CVIL differed substantially between infection states, offering preliminary evidence that these circulating markers could assist in distinguishing latent cases from active tuberculosis.

Latent tuberculosis infection represents a substantial worldwide health challenge because it establishes a large biological reservoir capable of generating future active disease and continuing transmission. Conventional diagnostic methods, such as the tuberculin skin test and interferon-gamma release assays, exhibit clear limitations in differentiating latent infection from active disease and cannot reliably predict disease progression. To address these diagnostic boundaries, investigators sought to evaluate circulating host serum RNA biomarkers using a real-time quantitative polymerase chain reaction assay.

The overall research population comprised 143 participants split between an initial investigation group and a secondary validation cohort. The primary study cohort included 93 individuals categorized into 20 patients with active tuberculosis, 54 individuals diagnosed with latent tuberculosis infection, and 19 participants evaluated through contact tracing. In addition, the researchers recruited an independent household-contact cohort containing 50 individuals who were monitored across six months of follow-up to test the reproducibility of candidate transcript detection patterns over time.

To assess biomarker candidates, the investigators separated serum samples from participants, extracted total RNA, and synthesized complementary DNA. The relative abundance of five target circulating transcripts—CXCL10, L6, CVIL, LIMD2, and ARSA1—was quantified through SYBR Green-based real-time qPCR. The team normalized expression measurements against the housekeeping reference transcript B2M and calculated relative transcript abundance using the standard 2^−ΔΔCt method, applying statistical analyses matched to data distribution.

Among the evaluated transcripts, CXCL10 proved to be the most frequently detected circulating marker across all primary cohorts, appearing in 100 percent of active tuberculosis patients, 92.6 percent of latent tuberculosis infection cases, and 89.5 percent of the contact tracing group. CXCL10 also demonstrated the most consistent detection profile within the independent 50-person household-contact cohort throughout the six-month follow-up period.

Statistical evaluations revealed significant differences in circulating transcript levels between the latent tuberculosis infection and active tuberculosis groups for CXCL10 (p = 0.019), L6 (p = 0.001), and CVIL (p = 0.001). For each of these three markers, relative transcript abundance was higher in participants with latent tuberculosis infection and comparatively lower in those with active tuberculosis. In contrast, the candidate transcripts LIMD2 and ARSA1 failed to demonstrate consistent or statistically significant variations between the diagnostic groups.

The study authors concluded that circulating serum CXCL10, L6, and CVIL transcripts provide preliminary candidate biomarkers for the early identification and discrimination of latent tuberculosis infection. However, they emphasized that the findings remain preliminary and require confirmation in larger, independently characterized patient groups that are longitudinally monitored before the clinical diagnostic utility of the assay can be established.

Subject of Research: Identification of circulating serum RNA biomarkers for latent tuberculosis infection using real-time qPCR

Article Title: Real-time PCR for the rapid identification of latent tuberculosis infection using circulating serum RNA transcripts as candidate biomarkers

Article References: Rathwita, R., Chiranthika, D., Bandara, T., Madegedara, D., & Magana-Arachchi, D. N. (2026). Real-time PCR for the rapid identification of latent tuberculosis infection using circulating serum RNA transcripts as candidate biomarkers. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14839-6

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14839-6

Keywords: latent tuberculosis infection, active tuberculosis, candidate biomarkers, real-time qPCR, CXCL10, L6 transcript, CVIL, LIMD2, ARSA1, B2M reference transcript, contact tracing, serum RNA, tuberculin skin test, interferon-gamma release assays, household contact cohort, disease progression, transcript abundance