PMID- 21563204
OWN - NLM
STAT- MEDLINE
DCOM- 20110930
LR  - 20211020
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 54
IP  - 2
DP  - 2011 Aug
TI  - Human leukocyte antigen in primary biliary cirrhosis: an old story now reviving.
PG  - 714-23
LID - 10.1002/hep.24414 [doi]
AB  - 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.
CI  - Copyright (c) 2011 American Association for the Study of Liver Diseases.
FAU - Invernizzi, Pietro
AU  - Invernizzi P
AD  - Center for Autoimmune Liver Diseases, Division of Internal Medicine, IRCCS 
      Istituto Clinico Humanitas, Rozzano, Milan, Italy. pietro.invernizzi@humanitas.it
LA  - eng
GR  - R01 DK056839-07/DK/NIDDK NIH HHS/United States
GR  - R01 DK056839-08/DK/NIDDK NIH HHS/United States
GR  - R01 DK056839-10/DK/NIDDK NIH HHS/United States
GR  - R01 DK056839-09/DK/NIDDK NIH HHS/United States
GR  - R01 DK056839-06A2/DK/NIDDK NIH HHS/United States
GR  - DK056839/DK/NIDDK NIH HHS/United States
GR  - R01 DK056839/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20110626
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Animals
MH  - Genetic Predisposition to Disease
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Liver Cirrhosis, Biliary/*genetics/*immunology
PMC - PMC3145017
MID - NIHMS295113
COIS- Disclosures: No conflicts of interest exist.
EDAT- 2011/05/13 06:00
MHDA- 2011/10/01 06:00
PMCR- 2012/08/01
CRDT- 2011/05/13 06:00
PHST- 2010/11/30 00:00 [received]
PHST- 2011/04/22 00:00 [accepted]
PHST- 2011/05/13 06:00 [entrez]
PHST- 2011/05/13 06:00 [pubmed]
PHST- 2011/10/01 06:00 [medline]
PHST- 2012/08/01 00:00 [pmc-release]
AID - 10.1002/hep.24414 [doi]
PST - ppublish
SO  - Hepatology. 2011 Aug;54(2):714-23. doi: 10.1002/hep.24414. Epub 2011 Jun 26.