title: Serum Autotaxin Activity Correlates With Pruritus in Pediatric Cholestatic Disorders.
abstract: OBJECTIVE
  Pruritus is a common symptom of cholestatic liver disorders. The present study aimed at evaluating autotaxin (ATX), a lysophospholipase recently identified as potential cause for cholestatic pruritus, in pediatric cholestatic diseases presenting with or without itching.
  
  
  METHODS
  A cohort of 45 children consisting of 14 patients experiencing itching (Alagille syndrome [n = 10], complete extrahepatic biliary atresia [n = 2], neonatal sclerosing cholangitis (n = 1), progressive familial intrahepatic cholestasis type 2 [n = 1]), 9 patients with bile acid synthesis defects (3β-hydroxy-C27-steroid-oxidoreductase [n = 7] and Δ-3-oxosteroid-5β-reductase deficiency [n = 2]), and 22 healthy children were studied. Serum ATX activity and total serum bile salt were determined enzymatically, ATX protein content was semiquantified by Western blotting. Using real-time polymerase chain reaction, ATX mRNA expression was studied in HepG2 cells treated with farnesoid-X-receptor agonists or vehicle.
  
  
  RESULTS
  Serum ATX activity was increased in pruritic children with Alagille and other cholestatic syndromes (mean ± standard deviation: 16.1 ± 4.3 nmol · mL · min) compared with children with nonpruritic cholestatic diseases with bile acid synthesis defects (10.4 ± 4.7 nmol · mL · min; P < 0.01) and healthy controls (7.6 ± 2.3 nmol · mL · min; P < 0.001). ATX protein levels closely correlated with serum ATX activity. Serum ATX activity and total serum bile salt showed a linear correlation with itch intensity (r = 0.66, P < 0.001 and r = 0.80, P < 0.001, respectively). No correlation was observed between ATX activity and bilirubin. ATX mRNA expression in HepG2 cells was not induced by farnesoid-X-receptor ligands.
  
  
  CONCLUSIONS
  Serum ATX activity correlated with itch intensity in children with cholestatic diseases. Bile salts did not increase ATX expression in vitro. ATX inhibitors may be useful antipruritic agents in pediatric cholestatic disorders.
authors.affiliation: *Department of Medicine I, Friedrich-Alexander-University of Erlangen, Erlangen, Germany †Tytgat Institute for Liver and Intestinal Research and Department of Hepatology & Gastroenterology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ‡Pediatric Hepatology Unit and National Reference Centre for Biliary Atresia, DHU Hepatinov, CHU Bicêtre, Assistance Publique-Hôpitaux de Paris, University Paris-Sud, Paris, and Inserm UMR-S1174, Orsay, France §Department of Surgery, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Kremer
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gonzales
authors.forename: Frank G
authors.initials: FG
authors.lastname: Schaap
authors.forename: Ronald P J
authors.initials: RP
authors.lastname: Oude Elferink
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jacquemin
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
mesh_terms: D016738:Alagille Syndrome / Q000097:blood / Q000503:physiopathology* / Q000628:therapy; D001656:Biliary Atresia / Q000097:blood / Q000503:physiopathology* / Q000628:therapy; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000503:physiopathology* / Q000628:therapy; D002779:Cholestasis / Q000097:blood / Q000503:physiopathology / Q000628:therapy; D002780:Cholestasis, Intrahepatic / Q000097:blood / Q000503:physiopathology* / Q000628:therapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D005602:France; D006785:Hospitals, University; D006801:Humans; D008297:Male; D010088:Oxidoreductases / Q000097:blood / Q000172:deficiency; D010727:Phosphoric Diester Hydrolases / Q000097:blood*; D010865:Pilot Projects; D011446:Prospective Studies; D011537:Pruritus / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D012720:Severity of Illness Index; D043202:Steroid Metabolism, Inborn Errors / Q000097:blood / Q000503:physiopathology / Q000628:therapy; D015854:Up-Regulation; D000099189:Lysophospholipase D
chemical_list: D015415:Biomarkers; D010088:Oxidoreductases; D010727:Phosphoric Diester Hydrolases; D000099189:Lysophospholipase D