Molecular markers of tuberculosis and their clinical relevance: a systematic review and meta-analysis

Since research on disease biomarkers of tuberculosis (TB) and latent tuberculosis infection (LTBI) provides hope for simple point-of-care testing, we aim to summarize and analyze the evidence for the clinical relevance of IFN-γ-inducible protein 10 (IP-10) and IFN-γ/interleukin 2 (IL-2) as diagnostic biomarkers for TB.

The search terms tuberculosis, tuberculous pleurisy, pulmonary tuberculosis, latent tuberculosis infection, biomarkers, markers, IFN-γ-inducible protein 10, IP-10, interleukin 2, and IL-2 were used to search the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu databases. The retrieval time was from the establishment of the database to September 2021. The Cochrane risk of bias tool was used to evaluate the quality of the included studies, and the meta-analysis was performed using RevMan 5.20.

A total of 9 articles were included for meta-analysis. The quality assessment showed that the overall quality of the included articles was met the requirements. The results showed that the overall sensitivity and specificity of IP-10 were 0.77 (95% CI, 0.71-0.82) and 0.84 (95% CI, 0.80-0.88), respectively. The overall sensitivity and specificity of IL-2 were 0.82 (95% CI, 0.74-0.89) and 0.95 (95% CI, 0.88-0.98), respectively. The areas under the curves (AUCs) of the IP-10 and IL-2 summary receiver operating characteristic (SROC) curves were 0.8592 and 0.9666, respectively.

The results of this systematic review and meta-analysis showed that IP-10 and IL-2 as biomarkers have good clinical relevance to TB and can be used for the clinical screening of high-risk TB populations. However, a prospective cohort study across multiple regions using a large sample size should also be conducted.