Directional immuno–metabolic signatures following severe trauma are associated with organ-specific clinical endpoints in a prospective cohort
4 affiliations
- 1Ludwig Boltzmann Institute for Traumatology, the Research Center in Cooperation with AUVA
- 2AUVA Trauma Center Salzburg, Department of Anesthesiology and Intensive Care Medicine, Academic Teaching Hospital of the Paracelsus Medical University
- 3Institute for Molecular Biotechnology, BOKU University
- 4Department of Anesthesiology and Intensive Care Medicine, AUVA Trauma Center Vienna
Abstract
Background: Severe trauma elicits evolving immune-metabolic responses that may differ across clinical endpoints. We characterized time-resolved innate and adaptive immune patterns associated with higher or lower endpoint odds during the first 96 h after injury.
Methods: Of 62 patients prospectively enrolled in the observational PRIME study (ISS >15), 52 met the prespecified analytical completeness criterion. Clinical and immune biomarkers were assessed at emergency room admission (ER), 24, 48, and 96 h. Time-point-specific quartile deviations were evaluated using logistic regression against microbiological culture positivity during hospitalization, creatinine-defined renal impairment, Berlin-defined ARDS of any severity, hepatic enzyme elevation, and four hemodynamic endpoints. Complementary sensitivity analyses and bootstrap resampling assessed the exploratory associations and their internal stability.
Results: Microbiological culture positivity was associated with lower admission base excess and temperature, reduced CD4/CD8 ratios and CD4 ⁺ T-cell proportions at 24–48 h, and lower monocyte measures with higher IL-8 at 96 h. The 96-h monocyte CBC/IL-8 combination showed an apparent within-cohort AUC of 0.78. Creatinine-defined renal impairment was associated with lower admission pH and base excess and a higher-IL-8/lower-CD4/CD8 combination (apparent AUC 0.88), alongside later myeloid and lymphocyte-related alterations. Berlin-defined ARDS showed predominantly low-odds associations, including higher early pH and phagocytic capacity; its 96-h combination of lower phagocyte CD64 expression and lower lymphocyte percentage yielded an apparent AUC of 0.80. Hepatic enzyme elevation showed low-odds associations involving higher 96-h monocyte HLA-DR expression and lower CD64 ⁺ phagocyte counts (apparent AUC 0.78). Hemodynamic endpoints showed distinct, endpoint-specific high-odds configurations. Bootstrap selection reproducibility was limited for the retained multivariable combinations.
Conclusion: The evaluated clinical endpoints were associated with distinct directional immune-metabolic configurations rather than a uniform inflammatory response. Their hypothesis-generating contribution lies in the endpoint-specific organization of established biological components across serial sampling points. These exploratory candidate signatures require independent validation before their potential clinical relevance can be established.
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BibTeX
@article{osuchowski2026directional,
title = {{Directional immuno–metabolic signatures following severe trauma are associated with organ-specific clinical endpoints in a prospective cohort}},
author = {Marcin Osuchowski and Gerhard Fritsch and Gebhard Woisetschläger and Johannes Grillari and Franz-Josef Nierscher and Alexandra Pomberger and Hubert Hetz and Heinz Steltzer and Roman Ullrich and Carolina Zeller and Behnaz Jafarmadar and Susanne Kerbl and Soheyl Bahrami and Johannes Zipperle},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1964036},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1964036/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Directional immuno–metabolic signatures following severe trauma are associated with organ-specific clinical endpoints in a prospective cohort
AU - Marcin Osuchowski
AU - Gerhard Fritsch
AU - Gebhard Woisetschläger
AU - Johannes Grillari
AU - Franz-Josef Nierscher
AU - Alexandra Pomberger
AU - Hubert Hetz
AU - Heinz Steltzer
AU - Roman Ullrich
AU - Carolina Zeller
AU - Behnaz Jafarmadar
AU - Susanne Kerbl
AU - Soheyl Bahrami
AU - Johannes Zipperle
PY - 2026
DA - 2026/10/28
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1964036
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1964036/full
AB - Background: Severe trauma elicits evolving immune-metabolic responses that may differ across clinical endpoints. We characterized time-resolved innate and adaptive immune patterns associated with higher or lower endpoint odds during the first 96 h after injury. Methods: Of 62 patients prospectively enrolled in the observational PRIME study (ISS >15), 52 met the prespecified analytical completeness criterion. Clinical and immune biomarkers were assessed at emergency room admission (ER), 24, 48, and 96 h. Time-point-specific quartile deviations were evaluated using logistic regression against microbiological culture positivity during hospitalization, creatinine-defined renal impairment, Berlin-defined ARDS of any severity, hepatic enzyme elevation, and four hemodynamic endpoints. Complementary sensitivity analyses and bootstrap resampling assessed the exploratory associations and their internal stability. Results: Microbiological culture positivity was associated with lower admission base excess and temperature, reduced CD4/CD8 ratios and CD4 ⁺ T-cell proportions at 24–48 h, and lower monocyte measures with higher IL-8 at 96 h. The 96-h monocyte CBC/IL-8 combination showed an apparent within-cohort AUC of 0.78. Creatinine-defined renal impairment was associated with lower admission pH and base excess and a higher-IL-8/lower-CD4/CD8 combination (apparent AUC 0.88), alongside later myeloid and lymphocyte-related alterations. Berlin-defined ARDS showed predominantly low-odds associations, including higher early pH and phagocytic capacity; its 96-h combination of lower phagocyte CD64 expression and lower lymphocyte percentage yielded an apparent AUC of 0.80. Hepatic enzyme elevation showed low-odds associations involving higher 96-h monocyte HLA-DR expression and lower CD64 ⁺ phagocyte counts (apparent AUC 0.78). Hemodynamic endpoints showed distinct, endpoint-specific high-odds configurations. Bootstrap selection reproducibility was limited for the retained multivariable combinations. Conclusion: The evaluated clinical endpoints were associated with distinct directional immune-metabolic configurations rather than a uniform inflammatory response. Their hypothesis-generating contribution lies in the endpoint-specific organization of established biological components across serial sampling points. These exploratory candidate signatures require independent validation before their potential clinical relevance can be established.
SN - 1664-3224
ER -