Circulating levels of soluble Fraktalkine in children with diarrhea associated Hemolytic Uremic Syndrome

PROULX, F; PALERMO, M; FERNANDEZ, G; TRACHTMAN, H; COMBADIERE, C

Toronto, Canada

Simposio; Toronto Critical Care Medicine Symposium; 2005

Introduction: We evaluated the role of a new chemotactic pathway called fractalkine (FKN), in the pathogenesis of diarrhea associated hemolytic uremic syndrome (D+HUS) caused by Shiga toxin producing Escherichia coli (STEC). FKN (CX3CLl) mediates direct leukocytes adhesion and also lead to chemotactism after cleavage of the chemokine domain by metalloproteases (ADAMS-10/ADAMS-17).   Methods: We measured in duplicate circulating levels of soluble fractalkine (sFKN) by sandwich ELISA (BAF365, AF365, R&D) in sera from normal controls (NC), including children (n=21) or adults (n=70); children with rotavirus enteritis (n=9), children with hemorrhagic colitis (HC) due to non 0157 pathogens (n=14); those uncomplicated E coli 0157:H7 HC (n=21), D+HUS (n=23), and children with chronic renal failure (CRF) unrelated to STEC infection (n=9).   Results: Concentrations (median, range), of sFKN were similar in healthy children 5.1 (0.2-7,498) versus adults 5.0 (0-223) pM. Serial measurements of sFKN on admission (day 0), day 1-2-8, did not vary overtime in children with uncomplicated 0157:H7 HC (ANOVA, p=NS). Concentrations of sFKN were as it follows: NC 5.1 (0.2-7,498) pM; viral 9.3 (0.3-2,613); Non-0157 HC 217.0 (42-11,109); 0157:H7 HC 17.0 (0.1-2,135); D+HUS 59.4 (0.1-10,164); CRF 7.2 (3.3-11,110); (Kruskall- Wallis; p <0.003). Orthogonal comparisons showed a trend for higher concentration of sFKN in children with Non-01'57 HC compared to 0157:H7 HC (p <0.003; a=0.0006). In the D+HUS group, levels of sFKN were comparable whether or not patients required dialysis: Dial+ (n=8), 36.0 (5.5-591) vs dial- (n=13), 132.0 (0.1­10,164) pM; p=NS.   Conclusions: Our data show very large variances in the shedding of sFKN under constitutive or inflammatory conditions. The enzymatic activity of metalloproteases (ADAMS-10/ADAMS-17) involved in FKN cleavage may be regulated by polymorphisms.