Human leukocyte antigen in primary biliary cirrhosis: An old story now reviving

Pietro Invernizzi

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Primary biliary cirrhosis (PBC) is an autoimmune biliary disease characterized by injury of small and medium size bile ducts, eventually leading to liver cirrhosis and death. Although the causes remain enigmatic, recent evidence has strengthened the importance of genetic factors in determining the susceptibility to the disease. Besides the strong heritability suggested by familial occurrence and monozygotic twins concordance, for decades there has not been a clear association with specific genes, with the only exception of a low risk conferred by a class II human leukocyte antigen (HLA) variant, the DRB1*08 allele, at least in some populations. The picture has become more complete when strong protective associations between PBC and the HLA DRB1*11 and DRB1*13 alleles were found in Italian and UK series. However, HLA genes have begun again to attract interest thanks to recent genome-wide association studies (GWAS), which clearly demonstrated that the major components of the genetic architecture of PBC are within the HLA region. As expected in a genetically complex disease, GWAS also identified several novel non-HLA variants, but it is worth noting that all of them are in immuno-related genes. In this review, the paradigmatic tale of what, and how, we learned about HLA genes in PBC will be retraced with particular focus on how GWAS are enabling a rewriting the story of PBC pathogenesis. These recent discoveries will not only drive functional studies but will also hold the promise of developing novel disease-specific treatments.

Original languageEnglish (US)
Pages (from-to)714-723
Number of pages10
JournalHepatology
Volume54
Issue number2
DOIs
StatePublished - Aug 2011

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Biliary Liver Cirrhosis
HLA Antigens
Genome-Wide Association Study
Genes
Alleles
HLA-D Antigens
Monozygotic Twins
Disease Susceptibility
Bile Ducts
Liver Cirrhosis
Autoimmune Diseases
Wounds and Injuries
Population

ASJC Scopus subject areas

  • Hepatology

Cite this

Human leukocyte antigen in primary biliary cirrhosis : An old story now reviving. / Invernizzi, Pietro.

In: Hepatology, Vol. 54, No. 2, 08.2011, p. 714-723.

Research output: Contribution to journalArticle

Invernizzi, Pietro. / Human leukocyte antigen in primary biliary cirrhosis : An old story now reviving. In: Hepatology. 2011 ; Vol. 54, No. 2. pp. 714-723.
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