Investigation of Primary Cilia in the Pathogenesis of Biliary Atresia

Abstract

Biliary atresia (BA) is an obliterative cholangiopathy presenting in the newborn period that leads to biliary cirrhosis and the need for liver transplantation in infancy unless treated early with a palliative Kasai portoenterostomy. BA is the most frequent indication for liver transplantation in children, but the pathogenesis remains unknown (1). Abnormalities of primary cilia are the cause of syndromes such as autosomal recessive polycystic kidney disease, in which renal cyst formation is associated with liver disease (2). The liver disease in ciliopathies is a ductal plate malformation leading either to congenital hepatic fibrosis or hepatic cyst development (3). In 10% to 20% of cases with BA (syndromic BA), there is an association with other specific developmental defects, including a laterality abnormality (situs inversus). Laterality is determined by primary cilia, and genes affecting laterality are involved in the organisation of cilial microtubules within the embryonal central node (4). In the present study we investigated children with BA who developed renal cysts to increase our understanding of the pathological process. We evaluated the effect of liver transplantation on cyst formation, assessed the role of primary cilia using fibrocystin as a cilial marker and looked for PKHD1 mutations in this group, and finally determined the function of their motile respiratory cilia.