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Significant joint-destructive association of HLA-DRB1*04:05 independent of DAS28 in rheumatoid arthritis
  1. Hideaki Tsuji1,
  2. Katsunori Ikari2,
  3. Koichiro Ohmura1,
  4. Koichiro Yano2,
  5. Moritoshi Furu3,
  6. Motomu Hashimoto3,
  7. Hiromu Ito4,
  8. Takao Fujii1,
  9. Wataru Yamamoto5,
  10. Atsuo Taniguchi2,
  11. Hisashi Yamanaka2,
  12. Tsuneyo Mimori1,
  13. Chikashi Terao1,6,7,8
  1. 1 Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
  2. 2 Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan
  3. 3 Department of the Control for Rheumatic Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan
  4. 4 Department of Orthopedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
  5. 5 Department of Health Information Management, Kurashiki Sweet Hospital, Kurashiki, Japan
  6. 6 Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  7. 7 Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan
  8. 8 The Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
  1. Correspondence to Dr Chikashi Terao, Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; a0001101{at}

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Preventing joint destruction is one of the challenges in rheumatoid arthritis (RA).1 Presence of two antibodies, namely, rheumatoid factor (RF) and cyclic citrullinated peptide antibodies (CCPs), is one of the major correlates of joint destruction.2 We recently showed the association between the progression of joint destruction and HLA-DRB1*04:05, which is independent from CCP positivity.3 HLA-DRB1*04:05 is one of shared epitope (SE) allele carrying common amino acid sequences at position 70–74 frequently found in Japanese and rarely observed in Europeans. Importantly, we showed that SE alleles other than DRB1*04:05 did not show independent associations from CCP.3

Based on the unique characteristics of HLA-DRB1*04:05, we hypothesised that HLA-DRB1*04:05 might lead to high disease activity not fully captured by Disease Activity Acore 28 (DAS28) and that it independently of DAS28 determines radiographic progression in patients with anti-CCP-positive RA (figure 1A).

Figure 1

HLA-DRB1*04:05 showed a significant association with SHS independently of DAS28. (A) …

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  • Handling editor Josef S Smolen

  • Contributors CT conceived the study design. HT and CT analysed the data. HT and CT wrote the main manuscript text. KY, KI, MH, MF, HI, TF, KO, AT, HY and TM contributed to collection of samples and/or data. KY and MF counted SHS score for the IORRA and KURAMA, respectively. WY aggregated the KURAMA database. All authors reviewed the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Kyoto University Graduate School of Medicine.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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