The Association between Circulating microRNAs and the Risk of Active Disease Development from Latent Tuberculosis...

Area of Science:

• Biochemistry and Molecular Biology
• Infectious Diseases
• Genetics

Background:

• Tuberculosis (TB) is a major global health threat, with a significant portion of infected individuals progressing from latent tuberculosis infection (LTBI) to active disease.
• Accurate biomarkers are crucial for identifying high-risk individuals for timely intervention and implementing effective End TB Strategies.
• Current methods for predicting active TB development from LTBI lack precision, necessitating the search for novel predictive markers.

Purpose of the Study:

• To identify circulating microRNAs (miRNAs) that can predict the progression from latent tuberculosis infection (LTBI) to active TB in a Chinese population.
• To evaluate the diagnostic potential of candidate miRNAs, individually and in combination with clinical factors, for predicting active TB development.

Main Methods:

• A nested case-control study design was employed, utilizing baseline samples from a prospective cohort tracking LTBI individuals.
• Circulating miRNAs were profiled using Agilent human miRNA microarray, with differentially expressed miRNAs validated by real-time quantitative PCR (RT-qPCR).
• Statistical analyses, including receiver operator characteristic (ROC) curve analysis, were performed to assess the predictive performance of identified miRNAs and their combinations with clinical variables like BMI and prior TB history.

Main Results:

• Microarray analysis identified six candidate miRNAs with significant differential expression between individuals who developed active TB and those who remained LTBI.
• RT-qPCR validation confirmed significantly lower baseline levels of hsa-miR-16-5p and hsa-miR-451a in the active TB case group compared to the LTBI control group (P < 0.001 for both).
• hsa-miR-451a, in combination with BMI and prior TB history, demonstrated the best predictive performance (AUC = 0.78), with a sensitivity of 80.82% and specificity of 79.22%.

Conclusions:

• Circulating hsa-miR-451a levels show significant potential as a non-invasive biomarker for predicting the development of active TB from LTBI in the studied Chinese population.
• The combination of hsa-miR-451a with clinical factors like BMI and TB history enhances predictive accuracy.
• Further validation in diverse populations and settings is warranted to confirm these findings and facilitate clinical application for precise TB prevention strategies.