title: Plasma levels of granulocyte elastase-alpha1-proteinase inhibitor complex in children with hemolytic uremic syndrome caused by verotoxin-producing Escherichia coli.
abstract: BACKGROUND
  Activated neutrophils play an important role in the pathogenesis of renal injury in humans and in experimental models of hemolytic uremic syndrome (HUS). To evaluate the clinical significance of the circulating granulocyte elastase-alpha1-proteinase inhibitor complex (GEPIC), which is a marker of neutrophil activation, we investigated the plasma concentrations of GEPIC in children with hemolytic uremic syndrome (HUS) associated with verotoxin-producing Escherichia coli (VTEC), VTEC gastroenteritis without HUS and in normal controls.
  
  
  METHODS
  Of 22 children (1-19 years of age; mean age 5.5 years) with VTEC infection, nine were diagnosed with HUS. Plasma GEPIC, soluble thrombomodulin (sTM) and thrombin-antithrombin-III complex (TAT) levels were measured by ELISA.
  
  
  RESULTS
  The number of polymorphonuclear leukocytes and the levels of plasma GEPIC in patients with HUS were significantly higher than those in non-HUS (9850+/-5091 vs. 5278+/-3327 /microL, P<0.05; 432.1+/-211.7 vs. 188.3+/-117.0 ng/mL, P<0.01) or control subjects (9850+/-5091 vs. 4728+/-1977 /microL, P<0.05; 432.1+/-211.7 vs. 105.9+/-51.1 ng/mL, P<0.001). Furthermore, plasma GEPIC levels showed a positive correlation with sTM (r = 0.522; P<0.01), a marker of endothelial cell injury, and TAT (r = 0.594; P<0.01), a marker of thrombin activity.
  
  
  CONCLUSIONS
  These results suggest that an increase in circulating GEPIC levels in patients with VTEC-associated HUS may be related to endothelial injury, which may possibly lead to a more severe episode of this disease.
authors.affiliation: Department of Pediatrics, Nara Prefectural Hospital, Nara, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Ishikawa
authors.forename: H
authors.initials: H
authors.lastname: Kamitsuji
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: A
authors.initials: A
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Umeki
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007223:Infant; D019272:Leukocyte Elastase / Q000097:blood*; D008297:Male; D018375:Neutrophil Activation / Q000502:physiology; D011379:Prognosis; D011480:Protease Inhibitors / Q000097:blood*; D022603:Shiga Toxins / Q000096:biosynthesis
chemical_list: D011480:Protease Inhibitors; D022603:Shiga Toxins; D019272:Leukocyte Elastase