ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2852

Evaluation of KIR3DL1/KIR3DS1 Association with Behçet’s Disease in Turkish Individuals

Burak Erer1, Elaine F. Remmers1, Masaki Takeuchi1, Colleen Satorius2, Duran Ustek3, Ilknur Tugal-tutkun4, Emire Seyahi5, Yilmaz Ozyazgan6, Ahmet Gul4, Daniel L. Kastner7 and Michael J. Ombrello8, 1Medical Genetics Branch, Inflammation Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 2National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 3Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey, 4Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey, 5Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey, 6Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey, 7Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, MD, 8Translational Genetics and Genomics Unit, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Vasculitis III

Session Type: Abstract Submissions (ACR)

Background/Purpose:

The Behçet’s disease (BD)-associated HLA-B type, HLA-B*51 (B*51), is a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells —KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity.  KIRs are inherited in evolutionarily conserved haplotypes in which KIR3DL1 and KIR3DS1 are mutually exclusive.  We therefore tested the hypothesis that KIR-regulated cytotoxic mechanisms contribute to BD by testing for association between the presence of KIR3DL1 and KIR3DS1 alleles in Turkish individuals.

Methods:

Turkish BD patients (n = 1,900) and controls (n = 1,779) were genotyped for the KIR3DL1 and KIR3DS1 alleles with two sequence-specific PCR assays.  Genotypes of 6,994 SNPs from the HLA region were determined with the Immunochip (Illumina) and used to impute the individuals’ HLA types using SNP2HLA and a reference panel of 5,225 European individuals.  A chi squared test for association was used to evaluate the contribution of KIR3DL1 and KIR3DS1 to BD. A P-value less than 0.05 was considered significant.

 

Results:

Classical HLA types were determined by imputation in all samples and types with posterior probability greater than 0.9 were included in analyses.  KIR3DL1 and KIR3DS1 genotypes were determined for 1799 of the cases and 1710 of the controls.  In these subjects, presence of the killing activating KIR3DS1 allele did not differ significantly between cases and controls (42.7% vs 41.0%, P = 0.29).  Furthermore, the activating allele did not appear to interact with HLA-B alleles.  It was present at similar frequencies in B*51-positive cases and controls (44.3% vs 43.0%, P = 0.63), in Bw4-positive cases and controls (43.0% vs 41.1%, P = 0.31), and in cases and controls bearing the Bw4 motif with isoleucine at position 80 (43.7% vs 41.4%, P = 0.32). Similarly, no disease association was found for the inhibitory KIR3DL1 allele in all the samples or in any of the HLA-B subsets.

Conclusion:

We found no association of BD with the presence of the KIR3D activating (KIR3DS1) or inhibitory (KIR3DL1) receptors, which together regulate cytotoxic cell activity through binding of a subset of HLA class I molecules, including the BD-associated HLA-B*51.  Due to the complexity of this locus (i.e. sequence variation, copy number variation), lack of association between BD and the presence/absence of KIR3DS1 or KIR3DL1 does not exclude a role for KIRs in the pathogenesis of BD.  Further studies of KIR3DL1/KIR3DS1 types and copy number variants, as well as of other KIRs, are warranted.

Disclosure:

B. Erer,
None;

E. F. Remmers,
None;

M. Takeuchi,
None;

C. Satorius,
None;

D. Ustek,
None;

I. Tugal-tutkun,
None;

E. Seyahi,
None;

Y. Ozyazgan,
None;

A. Gul,
None;

D. L. Kastner,
None;

M. J. Ombrello,
None.

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