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Abstract Number: 1936

The Human Leukocyte Antigen DRB1*13:02-DQB1*06:04-DPB1*04:01 Haplotype Is Closely Associated with Dermatomyositis Patients with Anti-CADM-140 (Melanoma Differentiation-Associated Protein 5: MDA5) Antibody

Yuji Hosono1, Chikashi Terao2, Ran Nakashima1, Yoshitaka Imura3, Naoichiro Yukawa4, Hajime Yoshifuji1, Motomu Hashimoto5, Koichiro Ohmura6, Takao Fujii7 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, 3Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 4Dept of Rheum & Clinical Immun, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 5The Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 6Rheumatology & Clin Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 7Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Antibodies, dermatomyositis and human leukocyte antigens (HLA)

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Session Information

Session Title: Muscle Biology, Myositis and Myopathies: Genetics, Autoantibodies and other Molecular Aspects of Idiopathic Inflammatory Myopathies and Models

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Recent studies have revealed that anti-CADM-140 (MDA5/IFIH1)-antibody positive dermatomyositis (DM) patients frequently develop acute or subacute progressive interstitial pneumonia (A/SIP) with poor prognosis. However, genetic background of anti-CADM-140-antibody positive DM is currently unclear. Here, we intended to analyze the relationship between specific human leukocyte antigen (HLA) alleles in anti-CADM-140-positive DM patients.

Methods:

Anti-CADM-140-antibody positive DM patients (CADMs, N=20) and healthy controls (HCs, N=2972) were enrolled in this study. Autoantibodies were screened using immunoprecipitation with [35S]methionine-labelled HeLa cells. HLA class I (A, B, and C) and class II (DRB1, DQA1, DQB1, and DPB1) genotyping was carried out with a highthroughput, high-resolution genotyping method (WAKFlow WAKUNAGA) by combining PCR and sequence-specific oligonucleotide probe protocols with the Luminex 100 xMAP flow cytometry dual-laser system to quantify fluorescently labelled oligonucleotides attached to colour-coded microbeads.Allele frequency was compared between CADMs and HCs by chi-square test or Fisher’s exact test. Haplotypes with frequency more than 10% in CADMs were analyzed for comparison between CADMs and HCs with chi-square test.

Results:

No specific HLA class I alleles show significant associations with CADMs.CADMs demonstrated higher allele frequencies of DRB1*1302 (15% vs 5.5%; with OR=2.73,0.0854), DQB1*0604 (12.5% vs 5.5%; with OR=2.5,P= 0.0114), and DPB1*0401 (12.5% vs 5%�G with OR=2.5,P= 0.03469) than HCs. However, no specific HLA alleles reached significant difference between CADMs and NCs due to lack of power. The observed distribution of HLA class II alleles among patients and controls suggested the notion that specific combinations of alleles at the DRB1, DQB1, and DPB1 loci are associated with the risk for CADMs. Haplotype analysis showed the frequency of the haplotype DRB1*13:02-DQB1*06:04-DPB1*04:01 was higher in CADMs than NCs (12.5% vs 3.6%;OR 3.79, 95%CI 1.47-9.76, P = 0.0030).

Conclusion:

HLA-DRB1*13:02-DQB1*06:04-DPB1*04:01 haplotype is closely associated with CADMs,suggesting that the production of anti-CADM-140 may be associated with a certain immunogenetive background.


Disclosure:

Y. Hosono,
None;

C. Terao,
None;

R. Nakashima,
None;

Y. Imura,
None;

N. Yukawa,
None;

H. Yoshifuji,
None;

M. Hashimoto,
None;

K. Ohmura,
None;

T. Fujii,
None;

T. Mimori,

Medical & Biological Laboratories, Co., Ltd.,

2,

Medical & Biological Laboratories, Co., Ltd,

8.

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