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A1810 - Large Scale Serum Protein Biomarker Discovery in Pediatric Sepsis
Author Block: A. Piliponsky1, K. Navalkar2, D. Sampson2, T. Yager2, S. Cermelli2, T. Seldon2, E. Sullivan3, J. Zimmerman3, L. Permut3, N. Shubin4; 1Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, United States, 2Immunexpress, Seattle, WA, United States, 3Seattle Children's Hospital, Seattle, WA, United States, 4Seattle Children s Research Institute, Seattle, WA, United States.
Sepsis is caused by a dysregulated host response to infection and can lead to life-threatening organ dysfunction. It is one of the most common causes of childhood death worldwide. Over the years, there have been many attempts to find biomarkers that can be used to diagnose sepsis. The problem is particularly challenging because, in its earliest manifestations (before significant organ damage has occurred) sepsis is difficult to distinguish from other, non-infectious causes of systemic inflammation with indices and sequelae that are physiologically and anatomically diffuse, and that fluctuate over short periods of time. The objective of this study was to conduct an expression screen using a modified aptamer-based technology in critically ill pediatric patients, to search for protein expression patterns that can discriminate sepsis from sterile systemic inflammatory response syndrome (SIRS). For this purpose, we used a cohort that consisted of 35 patients with clinical severe sepsis syndrome (CSSS) and 28 post-cardiac bypass (PCBP) patients presenting with sterile SIRS. The CSSS children had a confirmed or highly suspected infection (microbial culture orders, antimicrobial prescription), two or more systemic inflammatory response syndrome criteria (including temperature and leukocyte criteria), and at least cardiovascular ± pulmonary organ dysfunction. The CSSS and PCBP patients yielded ICU day 1 serum samples that were analyzed with an aptamer panel consisting of 1,305 highly specific protein-binding aptamers (SomaLogic, Boulder Colorado, USA). Using LIMMA analysis, a Benjamini-Hochberg multiple testing corrected p-value cut-off 1/n = 1/1305 = 0.0008, and an absolute fold-change ≥ 1.5, we identified 188 proteins that were differentially expressed between the PCPB and CSSS groups. Of these, 91 had higher values in sepsis relative to PCBP, and 97 had higher values in PCBP relative to sepsis. About half (91/188 = 48.4%) were also deemed as significant following BORUTA analysis. In summary, this aptamer scan led to the identification of 188 proteins that appear (at a 0.08 % false discovery rate) to significantly discriminate sepsis (CSSS) from SIRS (due to PCBP surgery) in pediatric patients. Further studies to establish biological meaning and clinical utility appear warranted.