Antimicrobial peptide LL37 and regulatory T cell associated with late-onset sepsis in very preterm infants

Ren Zhuxiao; Yang Shuo; Han Jiangxue; Pei Jingjun; Zhang Qi; Wang Zhu; Xu Fang; Yang Jie

doi:10.1016/j.isci.2024.109780

Antimicrobial peptide LL37 and regulatory T cell associated with late-onset sepsis in very preterm infants

iScience. 2024 Apr 18;27(5):109780. doi: 10.1016/j.isci.2024.109780. eCollection 2024 May 17.

Authors

Ren Zhuxiao^{1

2}, Yang Shuo³, Han Jiangxue^{1

2}, Pei Jingjun⁴, Zhang Qi⁵, Wang Zhu^{1

2}, Xu Fang^{1

2}, Yang Jie⁴

Affiliations

¹ Department of Neonatology, Guangdong Women and Children Hospital, Guangzhou, China.
² Guangzhou Medical University, Guangdong Neonatal ICU Medical Quality Control Center, National Key Clinical Specialty Construction Unit Guangzhou Medical University, Guangzhou 510000, Guangdong, China.
³ Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
⁴ Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
⁵ Department of Clinical Genetic Center, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou, China.

Abstract

Stem cell therapy may prevent late-onset sepsis (LOS) via antimicrobial peptide LL37 secretion and regulatory T cell (Treg) regulation. The early prediction of LOS is still a challenge. This study evaluated whether immunological state of LL37 or Tregs precedes LOS. We firstly analyzed the LL37 level, Treg proportion, and LOS incidence in very preterm infants treated with autologous cord blood mononuclear cells (ACBMNCs) in our previous trial. Then, we constructed a prediction model and built validation cohort. We found ACBMNC intervention reduced the incidence of LOS from 27.3% to 6.9% (p = 0.021). LL37 and Treg abundances were higher in the ACBMNCs group. The nomogram demonstrated that early-life Treg and LL37 characteristics were closely associated with LOS (area under the curve, AUC 0.936), with implications for early prediction and timely clinical management. This composite model was also helpful to evaluate the beneficial effect of ACBMNCs intervention on LOS, thus promoting translational research.

Keywords: Cell biology; Health sciences; Immunology; Stem cells research.