HLA and cytokine gene polymorphisms in biliary atresia

Donaldson, Peter; Clare, Michael; Constantini, Patrizia K.; Hadžić, Nedim; Mieli‐Vergani, Giorginia; Howard, E. R.; Kelley, Dympna

doi:10.1046/j.0106-9543.2002.01647.x

Cited by 51 publications

(28 citation statements)

References 36 publications

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“…Studies of a possible link between HLA type and BA have yielded conflicting results. [30][31][32] Because of the rarity of BA (approximately 1:8,000-18,000 live births) 33 and the paucity of liver and bile duct tissue available for research, the use of murine models provides valuable insight into the potential mechanisms of bile duct injury in this devastating disease. In this study, we show that the progressive bile duct injury is attributable in part to bile duct epithelia-specific T cell-mediated autoimmunity and that serum autoantibodies reactive to bile duct epithelial proteins are present in murine BA.…”

Section: Discussionmentioning

confidence: 99%

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia

et al. 2006

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Biliary atresia is an inflammatory fibrosclerosing lesion of the bile ducts that leads to biliary cirrhosis and is the most frequent indication for liver transplantation in children. The pathogenesis of biliary atresia is not known; one theory is that of a virus-induced, subsequent autoimmune-mediated injury of bile ducts. The aim of this study was to determine whether autoreactive T cells and autoantibodies specific to bile duct epithelia are present in the rotavirus (RRV)-induced murine model of biliary atresia and whether the T cells are sufficient to result in bile duct inflammation. In vitro analyses showed significant increases in IFN-␥-producing T cells from RRV-diseased mice in response to bile duct epithelial autoantigen. Adoptive transfer of the T cells from RRV-diseased mice into naïve syngeneic SCID recipients resulted in bile duct-specific inflammation. This induction of bile duct pathology occurred in the absence of detectable virus, indicating a definite response to bile duct autoantigens. Furthermore, periductal immunoglobulin deposits and serum antibodies reactive to bile duct epithelial protein were detected in RRV-diseased mice. In conclusion, both cellular and humoral components of autoimmunity exist in murine biliary atresia, and the progressive bile duct injury is due in part to a bile duct epithelia-specific T cell-mediated immune response. The role of cellular and humoral autoimmunity in human biliary atresia and possible interventional strategies therefore should be the focus of future research.

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Section: Discussionmentioning

confidence: 99%

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia

et al. 2006

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“…More recently, DNA genotyping has been adapted for HLA typing, yielding a greater number of HLA loci and alleles to be tested with much greater accuracy. Using DNA genotyping, Donaldson et al (67) found no HLA associations in 101 BA patients from the United Kingdom. It is clear that a large, multicentered study of HLA genotyping (including high resolution of HLA-class II) and a sample size calculated to generate statistically sound results is needed.…”

Section: T-cell-mediated Inflammation T-cell Activation Requires Thementioning

confidence: 99%

Unraveling the Pathogenesis and Etiology of Biliary Atresia

2005

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“…Several candidate-gene association studies have been conducted thus far on genes selected mainly for their role in inflammatory, immune and autoimmune responses and gene-expression analyses (12)(13)(14)(15). Indeed, gene-expression analyses on bile duct or liver tissues of mice and humans indicated that genes involved immune and autoimmune response may play a role in BA development (16)(17)(18)(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%