The role of proteomics in understanding biological mechanisms of sepsis

Abstract

Sepsis is a systemic inflammatory state caused by infection. Complications of this infection with multiple organ failure lead to more lethal conditions, such as severe sepsis and septic shock. Sepsis is one of the leading causes of US deaths. Novel biomarkers with high sensitivity and specificity may be helpful for early diagnosis of sepsis and for improvement of patient outcomes through the development of new therapies. Mass spectrometry-based proteomics offers powerful tools to identify such biomarkers and furthermore to give insight to fundamental mechanisms of this clinical condition. In this review, we summarize findings from proteomics studies of sepsis and how their applications have provided more understanding into the pathogenesis of septic infection. Literatures related to "proteomics", "sepsis", "systemic inflammatory response syndrome", "severe sepsis", "septic infection", and "multiple organ dysfunction syndrome" were searched using PubMed. Findings about neonatal and adult sepsis are discussed separately. Within the adult sepsis studies, results are grouped based on the models (e.g., human or animal). Across investigations in clinical populations and in rodent and mammalian animal models, biological pathways, such as inflammatory and acute phase response, coagulation, complement, mitochondrial energy metabolism, chaperones, and oxidative stress, are altered at the protein level. These proteomics studies have discovered many novel biomarker candidates of septic infection. Validation the clinical use of these biomarker candidates may significantly impact the diagnosis and prognosis of sepsis. In addition, the molecular mechanisms revealed by these studies may also guide the development of more effective treatments.

Gene Network for Identifying the Entropy Changes of Different Modules in Pediatric Sepsis

“…The incidence of pediatric sepsis is higher in developing country where pathogens readily invade children because of low birth weight, water and air pollution as well as insufficient immunization and nutrition [3,4]. Pediatric sepsis is a spectrum of disorders that mainly infected by bacteria, viruses, fungi, parasites or the toxic byproducts of these microorganisms [5,6]. Recently, many epidemiologic data reveal that a majority of severe sepsis attacks children without any predisposing condition [7].…”

“…Microarray data and genome-wide expression profiling also have been increasingly applied to identify novel pathways and therapeutic gene targets, sepsis-related biomarkers [6,[15][16][17]. A microarray-based study in children with septic shock demonstrated that development age is a major contributor to sepsis heterogeneity.…”

“…Although the diagnosis and management of sepsis in infants and children is mostly influenced by studies done in adults, many important considerations relevant to pediatrics need regard [8]. For the management of pediatric sepsis, intensive attention should be diverted to the age and immune capacity, site, severity and source of infection [6,8]. Exploring potential genes via different methods is essential for the prevention and treatment of pediatric sepsis.…”

Metabolomics in Sepsis and Its Impact on Public Health

“…[33]. Studies further down from the genome to the phenome, at the level of the epigenome, transcriptome, and proteome, have been, to some extent, successful in complementing and expanding our knowledge of disease pathophysiology [34-39]. Nevertheless, as transcriptional and translational elements exist in high numbers of variants and isoforms and are dynamically altered (with unknown time lags) through the interaction with the insulting pathogen, the results of transcriptomics and proteomics research in sepsis, though promising, need to be confirmed before they are applied at the bedside [40].…”

Early procalcitonin kinetics and adequate empiric antibiotic therapy in critically ill

“…This is in sharp contrast with the diagnostic power of certain biomarkers used in the world of "definitive" diseases, where several laboratory parameters have this ability. Nevertheless, there is still an ongoing search for better, new markers of inflammatory response and infection, with promising preliminary results [40].…”