Identification of CCL20 as a Prognostic Predictor for Severe Fever With Thrombocytopenia Syndrome Based on Plasma Proteomics

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS), a lethal tick-borne hemorrhagic fever, prompted our investigation into prognostic predictors and potential drug targets using plasma Olink Proteomics. Methods Employing the Olink assay, we analyzed 184 plasma proteins in 30 surv...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Journal of infectious diseases 2024-09, Vol.230 (3), p.741-753
Hauptverfasser: Zhang, Yue, Li, Lan, Liu, Yuanni, Zhang, Wei, Peng, Wenjuan, Zhang, Shuai, Qu, Renliang, Ma, Yuan, Liu, Zishuai, Ge, Ziruo, Zhou, Yanxi, Tian, Wen, Shen, Yi, Liu, Li, Duan, Jianping, Chen, Zhihai, Zhu, Liuluan
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Abstract Background Severe fever with thrombocytopenia syndrome (SFTS), a lethal tick-borne hemorrhagic fever, prompted our investigation into prognostic predictors and potential drug targets using plasma Olink Proteomics. Methods Employing the Olink assay, we analyzed 184 plasma proteins in 30 survivors and 8 nonsurvivors of SFTS. Validation was performed in a cohort of 154 patients with SFTS via enzyme-linked immunosorbent assay. We utilized the Drug-Gene Interaction Database to identify protein-drug interactions. Results Nonsurvivors exhibited 110 differentially expressed proteins as compared with survivors, with functional enrichment in the cell chemotaxis–related pathway. Thirteen differentially expressed proteins—including C-C motif chemokine 20 (CCL20), calcitonin gene–related peptide alpha, and pleiotrophin—were associated with multiple-organ dysfunction syndrome. CCL20 emerged as the top predictor of death, demonstrating an area under the curve of 1 (P = .0004) and 0.9033 (P < .0001) in the discovery and validation cohorts, respectively. Patients with CCL20 levels exceeding 45.74 pg/mL exhibited a fatality rate of 45.65%, while no deaths occurred in those with lower CCL20 levels. Furthermore, we identified 202 Food and Drug Administration–approved drugs targeting 37 death-related plasma proteins. Conclusions Distinct plasma proteomic profiles characterize SFTS cases with different outcomes, with CCL20 emerging as a novel, sensitive, accurate, and specific biomarker for predicting SFTS prognosis. We used the Olink Proteomics assay to investigate the plasma prognostic predictors of severe fever with thrombocytopenia syndrome and identified 110 differentially expressed proteins in nonsurvivors, mainly enriched in cell chemoattraction–related pathways. C-C motif chemokine 20 emerged as a notable predictor of death in patients with severe fever with thrombocytopenia syndrome. Graphical Abstract Graphical Abstract
ISSN:0022-1899
1537-6613
1537-6613
DOI:10.1093/infdis/jiae039