Serum Autotaxin Activity Correlates With Pruritus in Pediatric Cholestatic Disorders

Kremer A, Gonzales E, Schaap FG, Elferink RPJO, Jacquemin E, Beuers U (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Journal of Pediatric Gastroenterology and Nutrition Lippincott, Williams & Wilkins

Book Volume: 62

Pages Range: 530-5

Journal Issue: 4

DOI: 10.1097/MPG.0000000000001044

Abstract

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.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 (3?-hydroxy-C27-steroid-oxidoreductase [n = 7] and ?-3-oxosteroid-5?-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.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.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 with CRIS profile

Andreas Kremer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Involved external institutions

University of Paris 11 - Paris-Sud / Université Paris XI Paris-Sud FR France (FR) University of Amsterdam NL Netherlands (NL)

How to cite

APA:

Kremer, A., Gonzales, E., Schaap, F.G., Elferink, R.P.J.O., Jacquemin, E., & Beuers, U. (2016). Serum Autotaxin Activity Correlates With Pruritus in Pediatric Cholestatic Disorders. Journal of Pediatric Gastroenterology and Nutrition, 62(4), 530-5. https://dx.doi.org/10.1097/MPG.0000000000001044

MLA:

Kremer, Andreas, et al. "Serum Autotaxin Activity Correlates With Pruritus in Pediatric Cholestatic Disorders." Journal of Pediatric Gastroenterology and Nutrition 62.4 (2016): 530-5.

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