ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 893

Association Between Human Leukocyte Antigen-B’s Amino Acid Variation and Disease-Susceptibility To Takayasu’s Arteritis

Hajime Yoshifuji1, Chikashi Terao2, Kosaku Murakami3, Daisuke Kawabata3, Koichiro Ohmura1, Takao Fujii4, Yasushi Kawaguchi5, Hisashi Yamanaka5 and Tsuneyo Mimori1, 1Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 2Center for Genomic Medicine, Kyoto University, Kyoto, Japan, 3Dept of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 4Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 5Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Vasculitis I

Session Type: Abstract Submissions (ACR)

Background/Purpose: HLA-B52 and HLA-B51 are frequently seen in Asian population and are almost identical except two amino acid residues(the 63rd and 67th), but HLA-B52 is related with susceptibility to Takayasu’s arteritis (TAK) while HLA-B51 is related with susceptibility to Behçet’s disease.   To understand the mechanisms, we analyzed the variation of HLA-B amino acid sequences in TAK patients.

Methods: We collected DNA of 173 TAK patients from Kyoto University Hospital and Tokyo Women’s Medical University Hospital, genotyped their HLA-B alleles, and compared them with those of 2000 healthy controls.

Results: HLA-B52 was strongly related with TAK susceptibility (P < 0.000000000000001), while HLA-B51 was not (P = 0.39).   Analysis of HLA-B’s amino acid variations revealed that 171H (histidine at 171st position) compared with 171Y was a risk factor (P < 0.00000001), and 67F compared with 67notF (S, Y, C or M) was a protective factor (P < 0.0001) of TAK susceptibility.   Both the 171st and 67th amino acids are located at the groove of HLA-B protein, implying immune response is related to the pathogenesis.   Both HLA-B52 and HLA-B51 have the TAK-susceptible 171H.    While HLA-B52 has the TAK-susceptible 67S, HLA-B51 has the protective 67F.   That is a plausible reason why HLA-B51 was not related with TAK susceptibility.   Besides, we also searched for single nucleotide polymorphisms (SNPs) of non-HLA genes that related to TAK susceptibility and found several candidates of genes.

Conclusion: The difference of HLA-B’s 67th amino acid residue was supposed to divide the susceptibilities to TAK or Behçet’s disease.   Further analyses are needed to know what kind of peptides show affinities to the HLA-B’s groove.

Disclosure:

H. Yoshifuji,
None;

C. Terao,
None;

K. Murakami,
None;

D. Kawabata,
None;

K. Ohmura,
None;

T. Fujii,
None;

Y. Kawaguchi,
None;

H. Yamanaka,
None;

T. Mimori,
None.

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