Serum Autotaxin Activity Correlates with Pruritus in Pediatric Cholestatic Disorders

A. E. Kremer, E. Gonzales, F.G. Schaap, R. P. Oude Elferink, E. Jacquemin, U. Beuers

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4 Citations (Scopus)

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 (BASD) [3beta-hydroxy-C27-steroid-oxidoreductase (n = 7) and Delta-3-oxosteroid-5beta-reductase deficiency (n = 2)] and of 22 healthy children were studied. Serum ATX activity and total serum bile salt (TBS) were determined enzymatically, ATX protein content was semi-quantified by western blotting. Using real-time polymerase chain reaction, ATX mRNA expression was studied in HepG2 cells treated with farnesoid-X-receptor (FXR) agonists or vehicle. RESULTS: Serum ATX activity was increased in pruritic children with Alagille and other cholestatic syndromes (mean +/- SD: 16.1 +/- 4.3 nmol mL min) compared to non-pruritic cholestatic children with BASD (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 TBS 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 FXR ligands. CONCLUSIONS: Serum ATX activity correlated with itch intensity in cholestatic children. Bile salts did not increase ATX expression in vitro. ATX inhibitors may be useful antipruritic agents in paediatric cholestatic disorders.
Original languageEnglish
Pages (from-to)530-535
Number of pages6
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume62
Issue number4
DOIs
Publication statusPublished - Apr 2016

Keywords

  • autotaxin
  • pruritus
  • lysophosphatidic acid
  • children
  • cholestasis
  • bile salts
  • LYSOPHOSPHATIDIC ACID
  • URSODEOXYCHOLIC ACID
  • LIVER FIBROSIS
  • BILE-ACIDS
  • ITCH
  • DISEASE
  • CANCER

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