RGD Reference Report - Diabetes-independent increase of factor VII-activating protease activation in patients with Gram-negative sepsis (melioidosis). - Rat Genome Database

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Diabetes-independent increase of factor VII-activating protease activation in patients with Gram-negative sepsis (melioidosis).

Authors: de Jong, H K  Koh, G C K W  Bulder, I  Stephan, F  Wiersinga, W J  Zeerleder, S S 
Citation: de Jong HK, etal., J Thromb Haemost. 2015 Jan;13(1):41-6. doi: 10.1111/jth.12776. Epub 2014 Dec 6.
RGD ID: 36174011
Pubmed: PMID:25370187   (View Abstract at PubMed)
PMCID: PMC4309501   (View Article at PubMed Central)
DOI: DOI:10.1111/jth.12776   (Journal Full-text)


BACKGROUND: The plasma protease factor VII-activating protease (FSAP) can release nucleosomes from late apoptotic cells. Nucleosomes are markers of cell death, and extracellular cell-free DNA has been suggested to play an important role in inflammation and has been demonstrated to correlate with severity and outcome in sepsis patients.
OBJECTIVE: To investigate FSAP activation in patients suffering from Burkholderia pseudomallei infection (melioidosis), an important cause of Gram-negative sepsis in Southeast Asia. As diabetes mellitus (DM) is the most important risk factor for both melioidosis and sepsis, we were also able to examine the role of DM in FSAP activation in this cohort of patients.
METHODS: In a prospective observational study, complexes of FSAP with α2 -antiplasmin (AP) were assayed in 44 patients with melioidosis, 34 of whom were classified as diabetic. Eighty-two healthy subjects served as controls (52 with DM and 30 without).
RESULTS: FSAP-AP complex levels were markedly elevated in patients as compared with controls. The FSAP level increased by 16.82 AU mL(-1) in patients with melioidosis after adjustment for the effect of DM in the regression model. As expected, FSAP activation was correlated with nucleosome release (slope = 0.74). No difference in FSAP activation on admission was seen between survivors and non-survivors, but the extent of FSAP activation correlated with stage of the disease; repeated testing during convalescence showed a return towards normal values (day 0 vs. day 28, 4.16 AU mL(-1) , 95% confidence interval [CI] 1.42-12.22).
CONCLUSION: Patients with Gram-negative sepsis caused by B. pseudomallei have abundant FSAP activation, which significantly correlates with stage of disease. The presence of DM, however, does not influence the extent of FSAP activation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SERPINF1Humanmelioidosis  IEP protein:increased expression:plasma (human)RGD 
Serpinf1Ratmelioidosis  ISORGD:1342519protein:increased expression:plasma (human)RGD 
Serpinf1Mousemelioidosis  ISORGD:1342519protein:increased expression:plasma (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpinf1  (serpin family F member 1)

Genes (Mus musculus)
Serpinf1  (serine (or cysteine) peptidase inhibitor, clade F, member 1)

Genes (Homo sapiens)
SERPINF1  (serpin family F member 1)


Additional Information