PMID- 18340360
OWN - NLM
STAT- MEDLINE
DCOM- 20080716
LR  - 20221207
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Linking)
VI  - 9
IP  - 3
DP  - 2008 Apr
TI  - Combination of KIR and HLA gene variants augments the risk of developing birdshot 
      chorioretinopathy in HLA-A*29-positive individuals.
PG  - 249-58
LID - 10.1038/gene.2008.13 [doi]
AB  - Birdshot chorioretinopathy (BCR), a chronic ocular inflammatory disease with 
      characteristic choroidal lymphocytic infiltrates, has been strongly associated 
      with human leukocyte antigen (HLA)-A29. Although HLA-A29 occurs frequently in all 
      populations, BCR affects only a small percentage of HLA-A29-positive Caucasians, 
      indicating additional susceptibility factors for BCR. Discovery of HLA class 
      I-specific killer cell immunoglobulin-like receptors (KIR) led to a series of 
      epidemiological studies implicating KIR-HLA gene combinations in disease. Here, 
      we characterized KIR-HLA pairs in BCR patients and controls carrying HLA-A*29 as 
      well as controls lacking HLA-A*29. KIR-HLA pairs implicated for weak inhibition 
      (KIR2DL2/3+HLA-C1 and KIR3DL1+HLA-Bw4(T80)) in combination with activating KIR 
      genes associated with autoimmunity (KIR2DS2, 2DS3 and 2DS4) augment the risk of 
      developing BCR in HLA-A*29-positive individuals. The reciprocal association of 
      strong inhibitory pairs (KIR3DL1+HLA-Bw4(I80) and KIR2DL1+HLA-C2) in combination 
      with those implicated in protection from infection (KIR3DS1+HLA-Bw4(I80) and 
      KIR2DS1+HLA-C2) was observed in HLA-A*29-negative controls. These results suggest 
      that a profound effect of KIR2DS2/S3/S4 in the absence of strong inhibition may 
      enhance the activation of natural killer cells and T-cell subsets against 
      intraocular self-antigens, thereby contributing to pathogenesis of BCR.
FAU - Levinson, R D
AU  - Levinson RD
AD  - Ocular Inflammatory Disease Center, Jules Stein Eye Institute, David Geffen 
      School of Medicine at UCLA, University of California at Los Angeles, CA 
      90095-1652, USA.
FAU - Du, Z
AU  - Du Z
FAU - Luo, L
AU  - Luo L
FAU - Monnet, D
AU  - Monnet D
FAU - Tabary, T
AU  - Tabary T
FAU - Brezin, A P
AU  - Brezin AP
FAU - Zhao, L
AU  - Zhao L
FAU - Gjertson, D W
AU  - Gjertson DW
FAU - Holland, G N
AU  - Holland GN
FAU - Reed, E F
AU  - Reed EF
FAU - Cohen, J H M
AU  - Cohen JH
FAU - Rajalingam, R
AU  - Rajalingam R
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080313
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A29 antigen)
RN  - 0 (KIR2DS2 protein, human)
RN  - 0 (KIR3DL1 protein, human)
RN  - 0 (Receptors, KIR)
RN  - 0 (Receptors, KIR3DL1)
SB  - IM
MH  - Autoimmunity/*genetics/immunology
MH  - Base Sequence
MH  - Chorioretinitis/*genetics/immunology
MH  - France
MH  - Gene Expression Regulation/genetics/*immunology
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - HLA-A Antigens/*genetics/immunology
MH  - Humans
MH  - Killer Cells, Natural/*immunology/metabolism
MH  - Molecular Sequence Data
MH  - Receptors, KIR/*genetics/immunology
MH  - Receptors, KIR3DL1/genetics
MH  - Sequence Analysis, DNA
MH  - White People/genetics
EDAT- 2008/03/15 09:00
MHDA- 2008/07/17 09:00
CRDT- 2008/03/15 09:00
PHST- 2008/03/15 09:00 [pubmed]
PHST- 2008/07/17 09:00 [medline]
PHST- 2008/03/15 09:00 [entrez]
AID - gene200813 [pii]
AID - 10.1038/gene.2008.13 [doi]
PST - ppublish
SO  - Genes Immun. 2008 Apr;9(3):249-58. doi: 10.1038/gene.2008.13. Epub 2008 Mar 13.