PMID- 26290149
OWN - NLM
STAT- MEDLINE
DCOM- 20160623
LR  - 20220316
IS  - 1435-232X (Electronic)
IS  - 1434-5161 (Linking)
VI  - 60
IP  - 11
DP  - 2015 Nov
TI  - Associations of human leukocyte antigens with autoimmune diseases: challenges in 
      identifying the mechanism.
PG  - 697-702
LID - 10.1038/jhg.2015.100 [doi]
AB  - The mechanism of genetic associations between human leukocyte antigen (HLA) and 
      susceptibility to autoimmune disorders has remained elusive for most of the 
      diseases, including rheumatoid arthritis (RA) and type 1 diabetes (T1D), for 
      which both the genetic associations and pathogenic mechanisms have been 
      extensively analyzed. In this review, we summarize what are currently known about 
      the mechanisms of HLA associations with RA and T1D, and elucidate the potential 
      mechanistic basis of the HLA-autoimmunity associations. In RA, the established 
      association between the shared epitope (SE) and RA risk has been explained, at 
      least in part, by the involvement of SE in the presentation of citrullinated 
      peptides, as confirmed by the structural analysis of DR4-citrullinated peptide 
      complex. Self-peptide(s) that might explain the predispositions of variants at 
      11beta and 13beta in DRB1 to RA risk have not currently been identified. Regarding the 
      mechanism of T1D, pancreatic self-peptides that are presented weakly on the 
      susceptible HLA allele products are recognized by self-reactive T cells. Other 
      studies have revealed that DQ proteins encoded by the T1D susceptible DQ 
      haplotypes are intrinsically unstable. These findings indicate that the T1D 
      susceptible DQ haplotypes might confer risk for T1D by facilitating the formation 
      of unstable HLA-self-peptide complex. The studies of RA and T1D reveal the two 
      distinct mechanistic basis that might operate in the HLA-autoimmunity 
      associations. Combination of these mechanisms, together with other functional 
      variations among the DR and DQ alleles, may generate the complex patterns of 
      DR-DQ haplotype associations with autoimmunity.
FAU - Miyadera, Hiroko
AU  - Miyadera H
AUID- ORCID: 0000-0002-6805-414X
AD  - Research Center for Hepatitis and Immunology, National Center for Global Health 
      and Medicine, Chiba, Japan.
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Tokunaga, Katsushi
AU  - Tokunaga K
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20150820
PL  - England
TA  - J Hum Genet
JT  - Journal of human genetics
JID - 9808008
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Arthritis, Rheumatoid/genetics/immunology
MH  - Autoimmune Diseases/*genetics/*immunology
MH  - Diabetes Mellitus, Type 1/genetics/immunology
MH  - Genes, MHC Class II
MH  - Genetic Predisposition to Disease
MH  - HLA Antigens/*genetics
MH  - HLA-DQ Antigens/chemistry/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Haplotypes
MH  - Humans
MH  - Protein Stability
EDAT- 2015/08/21 06:00
MHDA- 2016/06/24 06:00
CRDT- 2015/08/21 06:00
PHST- 2015/05/11 00:00 [received]
PHST- 2015/07/22 00:00 [revised]
PHST- 2015/07/23 00:00 [accepted]
PHST- 2015/08/21 06:00 [entrez]
PHST- 2015/08/21 06:00 [pubmed]
PHST- 2016/06/24 06:00 [medline]
AID - jhg2015100 [pii]
AID - 10.1038/jhg.2015.100 [doi]
PST - ppublish
SO  - J Hum Genet. 2015 Nov;60(11):697-702. doi: 10.1038/jhg.2015.100. Epub 2015 Aug 
      20.