gms | German Medical Science

Objectives: Systemic inflammation results in impaired and insufficient control of a subsequent infection, thereby resulting in a systemic immunological imbalance in homeostasis and manifestation of sepsis. Despite numerous blood biomarkers identified by diverse proteomic approaches, there has been no conclusive investigation that has elucidated the relationship between these protein molecules and the clinical variables, which have been extensively employed in clinics. Multiplex and two single-plex miniaturized and parallelized sandwich IAs were performed on a bead-based system to determine the concentrations of 39 proteins. U-statistics was applied for multivariate data analysis. A total of 418 samples, derived from trauma and sepsis patients, were ext'pected to deliver a profile to predict outcome after major trauma. , which were selected on the basis of results from uni-variate studies demonstrating correlation with clinical indices of disease status as well as with the mortality of sepsis patients.

Methods: A total of 418 blood samples were obtained from 119 critically ill patients after surgery and/or trauma staying in the intensive care unit (ICU) 103 patients with trauma/SIRS (age: 64 +/-5) and 16 ICU postoperative/posttraumatic sepsis patients (age: 65 +/- 18) with different duration of illness were included). Three blood samples were collected from each trauma patient (before surgery, 1 day and 2 days after surgery); sepsis samples were collected daily over 4-15 days during the patients' stay in the ICU. All samples were profiled and characterized with a panel of 39 plasma parameters.

The following scores were included for the analysis: SAPSII (Simplified Acute Physiological Score II); SOFA (Sequential Organ Failure Assessment) Score; and Sepsis Score: graded, based on the international sepsis definitions. Four sets of multiplex and two single-plex miniaturized and parallelized sandwich IAs were performed on a bead-based system to determine concentration of 39 proteins.

Results and Conclusion: The analysis revealed that the molecular pattern of the clusters is both patient- and severity-dependent. Eight differentially expressed proteins (MMP-8, sFas, sICAM-1, sIL-2R, IL-1beta, IP-10, sTNF-RI, sTNF-RII) enabled sepsis to be distinguished from systemic inflammatory response syndrome (SIRS)/trauma. Multivariate U-statistics identified the expression patterns of IL-13 and GM-CSF in addition to a set of 7 plasma parameters (IL-1beta, IP-10, IL-8, MMP-3, sFas, sTNF-RI, sTNF-RII)The results support the correlation of plasma proteins with conventional clinical scores, thereby demonstrating that the identified biomarker panel is ready for extensive validation to predict sepsis outcome after major trauma.

A pattern of tri- or tetra-variate analysis of the specific biomarkers, i.e. IL-13 or Eotaxin, MMP7, sTNF-RI and IL-8, should support the clinical scores (SAPS II, SOFA and SEPSIS), for a highly valid prediction score.