Plasma Concentrations of sTREM-1 as Markers for Systemic Adverse Reactions in Subjects Treated With Weekly Rifapentine and Isoniazid for Latent Tuberculosis Infection

Tsai-Yu Wang; Jia-Yih Feng; Chin-Chung Shu; Susan Shin-Jung Lee; Chung-Yu Chen; Yu-Feng Wei; Chih-Bin Lin; Wei-Chang Huang; Wei-Juin Su; Shu-Min Lin

doi:10.3389/fmicb.2022.821066

Plasma Concentrations of sTREM-1 as Markers for Systemic Adverse Reactions in Subjects Treated With Weekly Rifapentine and Isoniazid for Latent Tuberculosis Infection

Front Microbiol. 2022 Mar 3:13:821066. doi: 10.3389/fmicb.2022.821066. eCollection 2022.

Authors

Tsai-Yu Wang^{1

2}, Jia-Yih Feng^{3

4}, Chin-Chung Shu⁵, Susan Shin-Jung Lee^{4

6}, Chung-Yu Chen⁷, Yu-Feng Wei⁸, Chih-Bin Lin⁹, Wei-Chang Huang^{10

11

12

13}, Wei-Juin Su³, Shu-Min Lin^{1

2}

Affiliations

¹ Department of Thoracic Medicine, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan.
² School of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁴ Faculty of Medicine, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan.
⁵ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁶ Division of Infectious Diseases, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
⁷ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan.
⁸ Division of Chest Medicine, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
⁹ Division of Chest Medicine, Department of Internal Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan.
¹⁰ Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
¹¹ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
¹² Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
¹³ School of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Abstract

Background: A regimen of once-weekly rifapentine plus isoniazid for 3 months (3HP) is an effective treatment for subjects with latent tuberculosis infection; however, no reliable biomarker exists for predicting systemic adverse reactions (SARs) to 3HP treatment.

Methods: This prospective, multi-center study evaluated the plasma concentrations of soluble triggering receptors expressed on myeloid cells (sTREM)-1 and sTREM-2 in subjects undergoing 3HP treatment and examined the associations between these biomarkers and SARs.

Results: This study enrolled 80 consecutive subjects receiving 3HP treatment, 25 of whom had SARs and 55 of whom did not. Subjects with SARs presented higher concentrations of sTREM-1 at baseline than those without SARs (240.1 ± 19.1 vs. 176.7 ± 9.4 pg/mL, P = 0.001). The area under the receiver operating characteristic curves revealed that day 1 plasma levels of sTREM-1 (0.708, 95% CI, 0.584-0.833, P = 0.003) and sTREM-2 (0.343, 95% CI, 0.227-0.459, P = 0.025) as well as the sTREM-1/sTREM-2 ratio (0.748, 95% CI, 0.638-0.858, P = 0.001) had modest discriminative power pertaining to the development of SARs. An sTREM-1 level exceeding the cut-off value (>187.4 pg/mL) (hazard ratio [HR], 6.15; 95% CI 1.67-22.70, P = 0.006) and a sTREM-2 below the cut-off value (<237.2 pg/mL) (HR, 4.46; 95% CI 1.41-14.1, P = 0.011) were independent predictors of SARs after controlling for other variables.

Conclusions: Plasma sTREM-1 and sTREM-2 levels are useful biomarkers for predicting SARs during 3HP treatment.

Clinical trial government: NCT04655794.

Keywords: LTBI; exacerbation; sTREM-1; sTREM-2; tuberculosis.

Associated data

ClinicalTrials.gov/NCT04655794