Plasma Elevations of Extracellular Matrix Collagens Are Predictive of Unfavorable Outcome after Trauma

Abstract

INTRODUCTION: The extracellular matrix is critical for intracellular communication, but the association between extracellular matrix integrity after trauma and clinical outcomes remains unexplored. Collagen type-6 alpha-3 chain (COL6A3) and collagen type-18 alpha-1 chain (COL18A1) are increased in patients’ plasma after hemorrhagic shock. We hypothesized that these increased concentrations of COL6A3 and COL18A1 are associated with adverse outcomes after severe injury. METHODS: Blood was collected from severely injured patients at a Level I trauma center as part of the COMBAT study. Plasma proteomics were performed using targeted liquid chromatography coupled with mass spectrometry. Spearman correlations, Mann-Whitney tests, and multiple linear regression were used to analyze association among injury, COL6A3, and COL18A1 levels, and outcomes. RESULTS: Patients with greater shock (lower base excess) on emergency department (ED) arrival had higher ED COL18A1 and 24-hour COL6A3 (both Spearman R –0.28, p < 0.05). Independently of NISS and base excess, higher ED COL18A1 and higher 24-hour COL6A3 were each associated with fewer ICU- and ventilator-free days (all p < 0.05, Figure 1). The effect of 24-hour COL6A3 on ICU-free days and ventilator-free days was also independent of ED COL18A1 (p < 0.05). Additionally, patients who developed ARDS had higher 24-hour COL6A3 (p < 0.05).CONCLUSION: Plasma measures of COL18A1 on ED arrival and COL6A3 at 24 hours are independent predictors of unfavorable outcome after injury. These collagen chains in the plasma are indicators of extracellular matrix destruction, and further study is needed to elucidate their potential role in inflammomodulatory signaling that mediates adverse outcomes.