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Association of Human Leukocyte Antigen with Interstitial Lung Disease in Rheumatoid Arthritis: A Protective Role for Shared Epitope

Author

Listed:
  • Hiroshi Furukawa
  • Shomi Oka
  • Kota Shimada
  • Shoji Sugii
  • Jun Ohashi
  • Toshihiro Matsui
  • Tatsuoh Ikenaka
  • Hisanori Nakayama
  • Atsushi Hashimoto
  • Hirokazu Takaoka
  • Yoshiyuki Arinuma
  • Yuko Okazaki
  • Hidekazu Futami
  • Akiko Komiya
  • Naoshi Fukui
  • Tadashi Nakamura
  • Kiyoshi Migita
  • Akiko Suda
  • Shouhei Nagaoka
  • Naoyuki Tsuchiya
  • Shigeto Tohma

Abstract

Introduction: Interstitial Lung Disease (ILD) is frequently associated with Rheumatoid Arthritis (RA) as one of extra-articular manifestations. Many studies for Human Leukocyte Antigen (HLA) allelic association with RA have been reported, but few have been validated in an RA subpopulation with ILD. In this study, we investigated the association of HLA class II alleles with ILD in RA. Methods: An association study was conducted on HLA-DRB1, DQB1, and DPB1 in 450 Japanese RA patients that were or were not diagnosed with ILD, based on the findings of computed tomography images of the chest. Results: Unexpectedly, HLA-DRB1*04 (corrected P [Pc] = 0.0054, odds ratio [OR] 0.57), shared epitope (SE) (P = 0.0055, OR 0.66) and DQB1*04 (Pc = 0.0036, OR 0.57) were associated with significantly decreased risk of ILD. In contrast, DRB1*16 (Pc = 0.0372, OR 15.21), DR2 serological group (DRB1*15 and *16 alleles) (P = 0.0020, OR 1.75) and DQB1*06 (Pc = 0.0333, OR 1.57, respectively) were significantly associated with risk of ILD. Conclusion: HLA-DRB1 SE was associated with reduced, while DR2 serological group (DRB1*15 and *16) with increased, risk for ILD in Japanese patients with RA.

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  • Hiroshi Furukawa & Shomi Oka & Kota Shimada & Shoji Sugii & Jun Ohashi & Toshihiro Matsui & Tatsuoh Ikenaka & Hisanori Nakayama & Atsushi Hashimoto & Hirokazu Takaoka & Yoshiyuki Arinuma & Yuko Okazak, 2012. "Association of Human Leukocyte Antigen with Interstitial Lung Disease in Rheumatoid Arthritis: A Protective Role for Shared Epitope," PLOS ONE, Public Library of Science, vol. 7(5), pages 1-7, May.
    • Handle: RePEc:plo:pone00:0033133
    DOI: 10.1371/journal.pone.0033133
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    1. Stephanie N Lewis & Elaine Nsoesie & Charles Weeks & Dan Qiao & Liqing Zhang, 2011. "Prediction of Disease and Phenotype Associations from Genome-Wide Association Studies," PLOS ONE, Public Library of Science, vol. 6(11), pages 1-10, November.
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    1. Shomi Oka & Hiroshi Furukawa & Aya Kawasaki & Kota Shimada & Shoji Sugii & Atsushi Hashimoto & Akiko Komiya & Naoshi Fukui & Satoshi Ito & Tadashi Nakamura & Koichiro Saisho & Masao Katayama & Shinich, 2014. "Protective Effect of the HLA-DRB1*13:02 Allele in Japanese Rheumatoid Arthritis Patients," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-12, June.
    2. HiwotBerhanu & Tefera Darge, 2020. "Pathophysiology of Rheumatoid Associated Lung Diseases," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 30(1), pages 22986-22992, September.
    3. Hiroshi Furukawa & Shomi Oka & Kota Shimada & Shoji Sugii & Atsushi Hashimoto & Akiko Komiya & Naoshi Fukui & Tatsuo Nagai & Shunsei Hirohata & Keigo Setoguchi & Akira Okamoto & Noriyuki Chiba & Eiich, 2013. "Association of Increased Frequencies of HLA-DPB1*05∶01 with the Presence of Anti-Ro/SS-A and Anti-La/SS-B Antibodies in Japanese Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-8, January.

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