Association of elevated plasma CCL5 levels with high risk for tic disorders in children

Hai-Zhen You; Jie Zhang; Yaning Du; Ping-Bo Yu; Lei Li; Jing Xie; Yunhui Mi; Zhaoyuan Hou; Xiao-Dong Yang; Ke-Xing Sun

doi:10.3389/fped.2023.1126839

Association of elevated plasma CCL5 levels with high risk for tic disorders in children

Front Pediatr. 2023 Apr 5:11:1126839. doi: 10.3389/fped.2023.1126839. eCollection 2023.

Authors

Hai-Zhen You¹, Jie Zhang², Yaning Du^{2

3}, Ping-Bo Yu¹, Lei Li⁴, Jing Xie¹, Yunhui Mi¹, Zhaoyuan Hou², Xiao-Dong Yang^{3

5

6}, Ke-Xing Sun¹

Affiliations

¹ Department of Traditional Chinese Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Clinical Research Center, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁶ Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

Abnormal levels of some peripheral cytokines have been reported in children patients with tic disorders (TDs), but none of these cytokines can be a biomarker for this disease. Our aim was to systemically profile differentially expressed cytokines (DECs) in the blood of TD patients, examine their associations with TD development, and identify from them potential biomarkers for the prediction and management of the risk for TDs. In this study, a cytokine array capable of measuring 105 cytokines was used to screen for DECs in the plasma from 53 comorbidity-free and drug-naïve TD patients and 37 age-matched healthy controls. DECs were verified by ELISA and their associations with TD development were evaluated by binary logistic regression analysis. Elevation of a set of cytokines was observed in TD patients compared with controls, including previously uncharacterized cytokines in tic disorders, CCL5, Serpin E1, Thrombospondin-1, MIF, PDGF-AA, and PDGF-AB/BB. Further analysis of DECs revealed a significant association of elevated CCL5 with TD development (p = 0.005) and a significant ROC curve for CCL5 as a risk factor [AUC, 0.801 (95% CI: 0.707-0.895), p < 0.0001].

Conclusion: This study identifies associations of a set of circulating cytokines, particularly CCL5 with TD development, and provides evidence that high blood CCL5 has potential to be a risk factor for TD development.

Clinical trial registration: identifier ChiCTR-2000029616.

Keywords: biomarker; cytokine; inflammation; risk factor; tic disorders.

Grants and funding

This study was supported by grants from National Key R&D Program of China (2021YFA1301400), Shanghai Municipal Science and Technology Major Project (ZD2021CY001), Shanghai Science and Technology Commission (21ZR1456300), Shanghai Children's Medical Center (LY-SCMC2020-03), and Shanghai Administration of Traditional Chinese Medicine (ZHYY-ZXYJHZX-201918) [H-ZY (2021-2023)-0206-08].