Soluble Fas and soluble Fas-ligand in children with Escherichia coli O157:H7–associated hemolytic uremic syndrome

Abstract

We measured soluble Fas-ligand (sFas-L) and soluble Fas (sFas) levels by sandwich enzyme-linked immunosorbeny assay and compared them among (1) healthy controls (n = 11), (2) children with hemorrhagic colitis (HC) caused by a non–verotoxin-producing pathogen (n = 23), (3) patients with uncomplicated Escherichia coli O157:H7 HC (n = 14), and (4) children with O157:H7-associated hemolytic uremic syndrome (HUS) (n = 24). Children with uncomplicated E coli O157:H7 HC and HUS were matched for duration of enteric prodrome before blood sample collection. We also compared sFas-L and sFas levels among patients with HUS according to severity of renal dysfunction; abnormally increased sFas-L levels were noted in only 4% of the children (n = 3). Abnormally high concentrations of sFas were noted in 9% of the children with HC caused by a non–verotoxin-producing pathogen, 29% of the patients with uncomplicated E coli O157:H7 HC, and 69% of the children with O157:H7-associated HUS. Compared with healthy controls, patients with HUS had twofold greater concentrations of sFas (P < 0.0001). Levels of sFas were not statistically different between 14 patients with uncomplicated O157:H7 HC and 14 children with HUS (8.2 ± 4.7 versus 11.0 ± 4.6 U/mL, respectively; P < 0.07) when matched for time after onset of enteritis (7.0 ± 3.7 versus 7.3 ± 3.8 days, respectively). Greater concentrations of sFas were noted in patients with HUS who developed oligoanuria (n = 10; P < 0.007), required peritoneal dialysis (n = 10; P < 0.007), or had a decreased glomerular filtration rate (n = 5; P < 0.002) 1 year later. Our data show that plasma concentrations of sFas but not sFas-L are abnormally increased in children with O157:H7 infections. Levels of sFas are associated with severity of renal dysfunction during HUS. Further studies are needed to clearly determine the role and origin of circulating sFas among children with infections caused by E coli O157:H7.