AUTHOR=Tang Yang , Yu Yanhua , Wang Quan , Wen Zilu , Song Ruixue , Li Yu , Zhou Yingquan , Ma Ruiying , Jia Hongyan , Bai Shaoli , Abdulsalam Harimulati , Du Boping , Sun Qi , Xing Aiying , Pan Liping , Wang Jianyun , Song Yanzheng 

TITLE=Evaluation of the IP-10 mRNA release assay for diagnosis of TB in HIV-infected individuals

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1152665

DOI=10.3389/fcimb.2023.1152665

ISSN=2235-2988

ABSTRACT=<p>HIV-infected individuals are susceptible to <italic>Mycobacterium tuberculosis</italic> (<italic>M.tb</italic>) infection and are at high risk of developing active tuberculosis (TB). Interferon-gamma release assays (IGRAs) are auxiliary tools in the diagnosis of TB. However, the performance of IGRAs in HIV-infected individuals is suboptimal, which limits clinical application. Interferon-inducible protein 10 (IP-10) is an alternative biomarker for identifying <italic>M.tb</italic> infection due to its high expression after stimulation with <italic>M.tb</italic> antigens. However, whether <italic>IP-10</italic> mRNA constitutes a target for the diagnosis of TB in HIV-infected individuals is unknown. Thus, we prospectively enrolled HIV-infected patients with suspected active TB from five hospitals between May 2021 and May 2022, and performed the IGRA test (QFT-GIT) alongside the <italic>IP-10</italic> mRNA release assay on peripheral blood. Of the 216 participants, 152 TB patients and 48 non-TB patients with a conclusive diagnosis were included in the final analysis. The number of indeterminate results of <italic>IP-10</italic> mRNA release assay (13/200, 6.5%) was significantly lower than that of the QFT-GIT test (42/200, 21.0%) (<italic>P</italic> = 0.000026). <italic>IP-10</italic> mRNA release assay had a sensitivity of 65.3% (95%CI 55.9% – 73.8%) and a specificity of 74.2% (95%CI 55.4% – 88.1%), respectively; while the QFT-GIT test had a sensitivity of 43.2% (95%CI 34.1% – 52.7%) and a specificity of 87.1% (95%CI 70.2% – 96.4%), respectively. The sensitivity of the <italic>IP-10</italic> mRNA release assay was significantly higher than that of QFT-GIT test (<italic>P</italic> = 0.00062), while no significant difference was detected between the specificities of these two tests (<italic>P</italic> = 0.198). The <italic>IP-10</italic> mRNA release assay showed a lower dependence on CD4<sup>+</sup> T cells than that of QFT-GIT test. This was evidenced by the fact that the QFT-GIT test had a higher number of indeterminate results and a lower sensitivity when the CD4<sup>+</sup> T cells counts were decreased (<italic>P</italic> &lt; 0.05), while no significant difference in the number of indeterminate results and sensitivity were observed for the <italic>IP-10</italic> mRNA release assay among HIV-infected individuals with varied CD4<sup>+</sup>T cells counts (<italic>P</italic> &gt; 0.05). Therefore, our study suggested that <italic>M.tb</italic> specific <italic>IP-10</italic> mRNA is a better biomarker for diagnosis of TB in HIV-infected individuals.</p>