BACKGROUND: Biliary atresia (BA) is a disorder during infancy with unknown etiology in which progression frequently leads to liver cirrhosis. Plasma proteome is characterized in this study. METHODS: Twelve paired plasma samples from 6 children with BA who received surgical correction at early stage and then liver transplantation at late stage of liver cirrhosis were studied. Plasma samples from 2 subjects without liver disorder were used as normal reference for 2-dimensional gel electrophoresis and for identification of protein spots by mass spectrometric analysis. Plasma samples from another 3 normal subjects (with a total of 5) were used for nephelometric quantification of immunoglobulin kappa light chain in comparison with patients' samples. RESULTS: Among the protein spots detected, ranging from 6 to 200 kDa mass with pIs of 3-10, significant up-regulation of immunoglobulin kappa light chain was found at the late stage of BA, which was subsequently confirmed by nephelometric analysis. Conversely, significant decrease of apolipoprotein (Apo) A-I and C-II, haptoglobin alpha2 and beta chain, and transthyretin were detected during the progression of BA. CONCLUSIONS: Increased immunoglobulin kappa light chain detected in late-stage BA characterizes adverse immune modulation in this disorder. Decreased apolipoproteins, haptoglobin and transthyretin levels might be potential markers of progressive liver injury, fibrosis and defective lipid metabolism in BA.
BACKGROUND:Biliary atresia (BA) is a disorder during infancy with unknown etiology in which progression frequently leads to liver cirrhosis. Plasma proteome is characterized in this study. METHODS: Twelve paired plasma samples from 6 children with BA who received surgical correction at early stage and then liver transplantation at late stage of liver cirrhosis were studied. Plasma samples from 2 subjects without liver disorder were used as normal reference for 2-dimensional gel electrophoresis and for identification of protein spots by mass spectrometric analysis. Plasma samples from another 3 normal subjects (with a total of 5) were used for nephelometric quantification of immunoglobulin kappa light chain in comparison with patients' samples. RESULTS: Among the protein spots detected, ranging from 6 to 200 kDa mass with pIs of 3-10, significant up-regulation of immunoglobulin kappa light chain was found at the late stage of BA, which was subsequently confirmed by nephelometric analysis. Conversely, significant decrease of apolipoprotein (Apo) A-I and C-II, haptoglobin alpha2 and beta chain, and transthyretin were detected during the progression of BA. CONCLUSIONS: Increased immunoglobulin kappa light chain detected in late-stage BA characterizes adverse immune modulation in this disorder. Decreased apolipoproteins, haptoglobin and transthyretin levels might be potential markers of progressive liver injury, fibrosis and defective lipid metabolism in BA.
Authors: Hongtao Wang; James P Malone; Petra Erdmann Gilmore; Alan E Davis; John C Magee; R Reid Townsend; Robert O Heuckeroth Journal: J Pediatr Gastroenterol Nutr Date: 2010-04 Impact factor: 2.839