Research & Innovation
Publications
Circulating CD38+ regulatory T cells are decreased in bone fracture non-union with chronic subclinical infection.
PMU Authors
Katharina Trenkwalder, Sandra Erichsen, Simon Hackl
All Authors
Pia Fehrenbach, Claudia Siverino, Katharina Trenkwalder, Sandra Erichsen, Simon Hackl, Ferdinand Weisemann, Gowrishankar Muthukrishnan, Martijn Riool, Cezmi A Akdis, Juan J Garcia-Vallejo, Sebastian A J Zaat, Esther C de Jong, Thomas Fintan Moriarty
Journal association
Scientific reports
Abstract
Fracture non-union represents a complex clinical challenge resulting from an incompletely understood interplay between mechanical and biological factors. Infection frequently contributes to non-union but many cases are misdiagnosed due to a lack of classical clinical symptoms. This study characterized peripheral blood mononuclear cells (PBMCs) from aseptic non-union (NU-AS, n = 24) and fracture-related infected non-union (NU-FRI, n = 20), and compare them to healed controls (H, n = 18). High-dimensional mass cytometry (CyTOF) revealed significant elevations of regulatory T cells (Tregs; p = 0.0028) and T helper 1 (Th1) cells (p = 0.0073), and reduced expression of the activation marker CD38 in CD4(+) T cells (p = 0.0016) and Tregs (p = 0.0017) in NU compared to H. In a subgroup analysis between NU-AS and NU-FRI, monocyte and CD38(+) Treg cell counts provided excellent diagnostic potential, with the combination achieving a sensitivity of 100% and a specificity of 91.7%. These findings highlight an important role of the activation marker CD38 in diagnosing chronic subclinical infection, which promises earlier identification of appropriate management of these patients.