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Combination of KIR‐HLA genotypes implicated in weak inhibition and autoimmunity augments risk for Birdshot Chorioretinopathy in HLA‐A29 positive individuals
Author(s) -
Rajalingam Raja,
Levinson Ralph D
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.850.4
Subject(s) - human leukocyte antigen , immunology , autoimmunity , biology , breakpoint cluster region , genotype , genetics , receptor , antigen , antibody , gene
HLA‐A29 is strongly associated with birdshot chorioretinopathy (BCR), a chronic ocular inflammatory disease with characteristic choroidal lymphocytic infiltrates. 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‐A29 as well as controls lacking HLA‐A29. We found that combination of KIR‐HLA genotypes implicated for weak inhibition (KIR2DL2/3+HLA‐C1 and KIR3DL1+HLA‐Bw4T80) and autoimmunity (KIR2DS2/S3/S4) augments the risk of developing BCR in HLA‐A29 positive individuals. The reciprocal association of strong inhibitory pairs (KIR3DL1+HLA‐Bw4I80 and KIR2DL1+HLA‐C2) in combination with those implicated in protection from infection (KIR3DS1+HLA‐Bw4I80 and KIR2DS1+HLA‐C2) was observed in HLA‐A29‐negative controls.