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Exploratory cluster analysis of IL2Ra and associated biomarkers and complications after blunt chest trauma
Krista L Haines1, Renhua Li, Scott Grey
1From the Division of Trauma and Acute Care Surgery, Department of Surgery (K.L.H., S.A., J.S.F.-M.), Duke University Medical Center, Durham, North Carolina; Department of Surgery (R.L., S.G., H.E.K., E.G., M.R., S.S.), Uniformed Services University of the Health Sciences, Bethesda, Maryland; Henry M. Jackson Foundation for the Advancement of Military Medicine (R.L., S.G., H.E.K., E.G., M.R.), Bethesda, Maryland; Surgical Critical Care Initiative (K.L.H., R.L., S.G., H.E.K., E.G., C.A., M.R., M.J., S.S., S.A., A.K., E.E., J.S.F.-M.), Bethesda, Maryland; Clinical Research Institute (C.A.), Substrate Services Core Research Support (M.J.), and Department of Surgery (A.K.), Duke University, Durham, North Carolina; and Walter Reed National Military Medical Center (E.E.), Bethesda, Maryland.
Background:
Rib fractures compromise approximately 40% of all fractures in the United States. Despite their prevalence, the relationship between rib fractures, solid organ injuries, and immune responses remains poorly understood. This exploratory study investigates the immunological profile associated with pulmonary and renal complications in rib fracture patients using data from our Surgical Critical Care Initiative Clinical Data Repository. The aim is to correlate distinct cytokine/chemokine profiles with high-energy rib fracture patterns, such as first rib fracture, and associated complications, potentially providing predictive biomarkers for patient outcomes.
Methods:
Clinical and demographic data on patients with rib fractures were extracted from Surgical Critical Care Initiative Clinical Data Repository. Patients were categorized based on the presence or absence of complications. A comprehensive panel of 46 inflammation and tissue repair biomarkers was measured using the Meso Scale Discovery platforms. Principal component analysis was used to reduce the dimensionality of the cytokine data. Statistical and machine learning models assessed the association between biomarker patterns, rib fracture localization, and complications. Logistic regression models with high discriminative performance were developed for first rib fractures (high energy transfer), lung injury, and pneumonia.
Results:
Among 150 rib fracture patients, 73 had complications. Cytokine analysis revealed two distinct clusters: Cluster 1, associated with pro-inflammatory responses and tissue repair, and Cluster 2, linked with anti-inflammatory responses, angiogenesis, and immunometabolism. Predictive models demonstrated strong validity (area under the curve, >0.90) and identified key variables such as the cytokine IL2Ra, significantly associated with acute kidney injury, acute lung injury, and pulmonary complications post-rib fractures, particularly first rib fractures.
Conclusion:
IL2Ra release is significantly correlated with high-energy transfer injuries like first rib fractures, indicating a bidirectional relationship between these fractures and the immune response. Furthermore, a hierarchical relationship exists among clinical complications, with kidney and lung injuries frequently preceding pneumonia. These findings underscore the potential utility of integrating immunological markers into clinical decision-support frameworks for personalized therapeutic interventions.
Level Of Evidence:
Prognostic and Epidemiological; Level IV.
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