Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased concentrations of extracellular chromatin are observed in cancer, sepsis, and inflammatory autoimmune diseases like systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). In SLE and RA, extracellular chromatin may behave as a danger-associated molecular pattern (DAMP). Polymorphonuclear neutrophils (PMN) are described as typical pro-inflammatory cells but possess also immunoregulatory properties. They are activated in SLE and RA but surprisingly remain moderately studied in these diseases, and especially the disease-associated stimuli triggering PMN activation are still not completely characterized. PMN express plasma membrane carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 8 (CD66b) and secrete a soluble form of CEACAM8 after activation. Soluble CEACAM8 has in turn immunoregulatory functions. However, few natural stimuli inducing soluble CEACAM8 secretion by PMN have been identified. Here we demonstrate for the first time that extracellular chromatin triggers secretion of soluble CEACAM8 by primary human PMN. Priming of PMN was not required. Secretion was associated with activation of PMN. Similar induction of soluble CEACAM8 release was observed with purified mono-nucleosomes as well as long chromatin fragments and occurred in a time-dependent and concentration-dependent manner. Results indicate that chromatin induces both neo-synthesis of soluble CEACAM8 and release of soluble CEACAM8 through degranulation. In addition, we report the presence of soluble CEACAM8 at high concentration in the synovial fluid of RA patients. Thus, we describe here a novel mechanism by which a natural DAMP, with inflammatory properties in SLE and RA, induces soluble CEACAM8 secretion by activated PMN with potential immunoregulatory consequences on other immune cells, including PMN.
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PMID:Extracellular Chromatin Triggers Release of Soluble CEACAM8 Upon Activation of Neutrophils. 3125 30

Accurate diagnosis of sepsis remains challenging, new markers or combinations of markers are urgently needed. In the present study, we screened differentially expressed genes (DEGs) between sepsis and non-sepsis blood samples across three previously published gene expression data sets. Common upregulated and downregulated DEGs were ranked according to their average functional similarity. The ten genes (OLFM4, ORM1, CEP55, S100A12, S100P, LRG1, CEACAM8, MS4A4A, PLSCR1, and IL1R2) with the largest average functional similarity among the common upregulated genes and another ten genes (THEMIS, IL2RB, CD2, IL7R, CD3E, KLRB1, PVRIG, CCRR3, TGFBR3, and PLEKHA1) with the largest average functional similarity among the common downregulated genes were separately identified as the upregulated crucial gene set and the downregulated crucial gene set. Gene set variation analysis (GSVA) was used to obtain the GSVA index of each sample against the two crucial gene sets. Both the two crucial GSVA indexes may be robust markers for sepsis with high area under ROC curve. The diagnostic utility of the upregulated GSVA index was validated in another independent data set. Functional analyses revealed several sepsis-related pathways. In conclusion, we proposed two sepsis-related gene sets across multiple data sets and created two GSVA indexes with promising diagnostic value.
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PMID:Two gene set variation indexes as potential diagnostic tool for sepsis. 3265 6