Coagulation and complement protein differences between septic and uninfected systemic inflammatory response syndrome patients

BACKGROUND: Systemic inflammatory response syndrome (SIRS) represents a host response to various insults. Recent advances have demonstrated an interconnection between inflammation, complement, and coagulation. This experiment was designed to evaluate differences in plasma protein profiles between clinically identical patients: septic versus uninfected SIRS patients, prior to clinical diagnosis of infection. METHODS: Patients admitted to an intensive care unit of a major university, meeting two of four SIRS criteria were followed prospectively for development of sepsis. Plasma samples were collected daily and divided into two groups: a preseptic group that subsequently developed sepsis and a SIRS group that remained uninfected. Protein profiling was accomplished by three-dimensional liquid chromatography fractionation with electrospray ion trap mass spectrometry after immunodepletion of abundant proteins and a trypsin digest. Spectra peaks were identified using Agilent Technologies Spectrum Mill Workbench software. Relevance to biologic pathways was analyzed and statistical significance determined with DAVID 2.1 available at the National Institutes of Health. RESULTS: A total of 134 unique proteins were significantly different between groups. Thirty-two of these (23.5%) mapped to the complement and coagulation cascade (KEGG), 10 (7.5%) mapped to classic complement pathway; 11 (8.2%) mapped to complement pathway, and 8 (6.0%) mapped to lectin binding complement pathway (Biocarta). These pathways were all significantly (p <0.0001) over-represented in sepsis patients compared to SIRS-only patients. CONCLUSION: Using novel mass spectrometry methodology, we were able to demonstrate differential protein profiles in septic versus uninfected SIRS patients prior to clinical diagnosis of sepsis.