Continuous evaluation of changes in the serum proteome from early to late stages of sepsis caused by Klebsiella pneumoniae

Abstract

Serum protein profiles of patients with bacterial sepsis from the day of diagnosis until recovery/mortality were compared from early to late stages in response to severe sepsis using two dimensional electrophoresis. The proteins exhibiting changes during the course of sepsis (20‑28 day mortality) were selected and identified by matrix‑assisted laser desorption ionization‑time of flight‑tandem mass spectrometry. Among the proteins identified, haptoglobin (Hp), transthyretin (TTR), orosomucoid 1/α1 acid glycoprotein (ORM1), α1 antitrypsin (A1AT), serum amyloid A (SAA) and S100A9 exhibited differential expression patterns between survivors (S; n=6) and non‑survivors (NS; n=6), particularly during the early stages of sepsis. Expression factors (EFs), taken as the ratio between the NS and S during early stages, showed ratios of Hp, 0.39 (P≤0.012); TTR, 3.96 (P≤0.03); ORM1, 0.69 (P≤0.79); A1AT, 0.92 (P≤0.87) and SAA, 0.69 (P≤0.01). S100A9, an acute phase protein, exhibited an EF ratio of 1.68 (P≤0.004) during the end stages of sepsis. A delayed rise in levels was observed in Hp, A1AT, ORM1, S100A9 and SAA, whereas TTR levels increased during the early stages of sepsis in NS. Analysis of inflammatory responses in the early stages of sepsis revealed increased mRNA expression in leukocytes of interleukin (IL)‑6 (EF, 2.50), IL‑10 (EF, 1.70) and prepronociceptin (EF, 1.6), which is a precursor for nociceptin in NS compared with S, and higher Toll‑like receptor‑4 (EF, 0.30) levels in S compared with NS. Therefore, a weaker acute phase response in the early stages of sepsis in NS, combined with an inefficient inflammatory response, may contribute to sepsis mortality.

Hepatocyte-like cells reveal novel role of SERPINA1 in transthyretin amyloidosis

“…SERPINA1 expression was inversely correlated with TTR levels after knockdown, suggesting a mutual dependence of both genes. Intriguingly, investigations of serum TTR and SERPINA1 levels in cells of patients suffering various diseases indicates opposed levels of expression (Bag et al, 2014;Fatima et al, 2017;Raju M. et al, 2016). Although the exact molecular regulation of opposite expression levels remains to be unraveled, IL-6 driven induction of gene expression following inflammation might play a role.…”

S100A8/A9 in Inflammation

“…S100A9 expression is significantly upregulated in the early stage of Klebsiella pneumoniae infection-induced sepsis. In septicemia-induced septic shock, the expression of S100A9 is continuously increased until the patient’s death ( 5 ). Deficiency of S100A8/A9 in mice could promote the progression of pneumonia caused by Staphylococcus aureus infection ( 6 ).…”

Bioinformatical Analysis of Organ-Related (Heart, Brain, Liver, and Kidney) and Serum Proteomic Data to Identify Protein Regulation Patterns and Potential Sepsis Biomarkers

“…However, sepsis represents a continuum ranging from simple infection and bacteraemia to life threatening septic shock with multiple organ dysfunction. As sepsis is a highly dynamic process, protein alterations may vary during the different stages of the disease [ 7 ]. Compared with genetic analyses, proteomics can give direct insight into protein expression and not only in an indirect way as would be possible by studying gene regulation.…”