Diagnostic Performance of a Novel CXCL10 mRNA Release Assay for Mycobacterium tuberculosis Infection

Liping Pan; Mailing Huang; Hongyan Jia; Guofang Deng; Yu Chen; Rongrong Wei; Mingxia Zhang; Xin Li; Qi Sun; Mutong Fang; Pengfei Ren; Aiying Xing; Qi Chen; Xinxin Li; Boping Du; Tao Chen; Mengqiu Gao; Zongde Zhang

doi:10.3389/fmicb.2022.825413

Diagnostic Performance of a Novel CXCL10 mRNA Release Assay for Mycobacterium tuberculosis Infection

Front Microbiol. 2022 Mar 30:13:825413. doi: 10.3389/fmicb.2022.825413. eCollection 2022.

Authors

Liping Pan¹, Mailing Huang², Hongyan Jia¹, Guofang Deng³, Yu Chen⁴, Rongrong Wei¹, Mingxia Zhang⁵, Xin Li⁶, Qi Sun¹, Mutong Fang³, Pengfei Ren⁴, Aiying Xing¹, Qi Chen⁵, Xinxin Li⁴, Boping Du¹, Tao Chen³, Mengqiu Gao², Zongde Zhang¹

Affiliations

¹ Beijing Chest Hospital, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical University, Beijing, China.
² Department of Tuberculosis, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical University, Beijing, China.
³ Department of Pulmonary Medicine, The Third People's Hospital of Shenzhen, Shenzhen, China.
⁴ Department of Tuberculosis, Henan Provincial Infectious Disease Hospital, Zhengzhou, China.
⁵ Laboratory Medical Center, The Third People's Hospital of Shenzhen, Guangdong Key Lab of Emerging Infectious Diseases, Shenzhen, China.
⁶ Laboratory Medical Center, Henan Provincial Infectious Disease Hospital, Zhengzhou, China.

Abstract

One-fourth of the world's population has been infected with Mycobacterium tuberculosis (M.tb). Although interferon-gamma release assays (IGRAs) have been shown to be valid methods for identifying M.tb infection and auxiliary methods for diagnosis of active tuberculosis (TB), lower sensitivity and higher indeterminate rate were often detected among immunosuppressed patients. IP-10 was an alternative biomarker due to the higher expression level after M.tb antigen stimulation, but whether CXCL10 mRNA (the gene that transcribes for the IP-10 protein) can be used as a target for M.tb infection diagnosis was limited. Therefore, we aimed to evaluate the performance of a novel M.tb-specific CXCL10 mRNA release assay in diagnosis of M.tb infection. Suspected TB patients and healthy controls were prospectively recruited between March 2018 and November 2019 from three hospitals in China. CXCL10 mRNA release assay and traditional interferon-gamma release assay (T-SPOT.TB) were simultaneously performed on peripheral blood. Of the 1,479 participants enrolled in the study, 352 patients with definite TB and 153 healthy controls were analyzed. CXCL10 mRNA release assay provided a sensitivity of 93.9% (95% CI = 90.8-96.2%) and a specificity of 98.0% (95% CI = 94.3-99.6%) in the diagnosis of M.tb infection, respectively, while T-SPOT.TB gave a sensitivity of 94.5% (95% CI = 91.5-96.6%) and a specificity of 100% (95% CI = 97.6-100.0%) in the diagnosis of M.tb infection, respectively. The diagnostic performance of CXCL10 mRNA release assay was consistent with T-SPOT.TB, with a total coincidence rate of 95.0% (95% CI = 93.0-96.9%) and a Cohen's kappa value of 0.89 (0.84-0.93, p < 0.001). However, among TB patients with HIV co-infection (n = 14), CXCL10 mRNA release assay presented significantly higher positive rate [92.9% (66.1-99.8%) vs. 61.5% (31.6-86.1%), p = 0.029] than those of T-SPOT.TB. These results suggested that M.tb-specific CXCL10 mRNA was a novel and useful target in the diagnosis of M.tb infection.

Keywords: CXCL10; M.tb infection; T-SPOT.TB; mRNA; molecular diagnosis; tuberculosis.