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Quantitative effect of HLA-DRB1 alleles to ACPA levels in Japanese rheumatoid arthritis: no strong genetic impact of shared epitope to ACPA levels after stratification of HLA-DRB1*09:01
  1. Chikashi Terao1,2,
  2. Katsunori Ikari3,
  3. Koichiro Ohmura2,
  4. Taku Suzuki3,
  5. Takuji Iwamoto3,
  6. Kiyoshi Takasugi4,
  7. Hiroo Saji5,
  8. Atsuo Taniguchi3,
  9. Shigeki Momohara3,
  10. Hisashi Yamanaka3,
  11. Fumihiko Matsuda1,6,7,
  12. Tsuneyo Mimori2
  1. 1Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
  2. 2Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
  3. 3Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
  4. 4Dohgo Spa Hospital, Matsuyama, Japan
  5. 5HLA Laboratory, Kyoto, Japan
  6. 6CREST Program, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan
  7. 7Institut National de la Sante et de la Recherche Medicale (INSERM) Unite U852, Kyoto University Graduate School of Medicine, Kyoto, Japan
  1. Correspondence to Chikashi Terao, Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; a0001101{at}kuhp.kyoto-u.ac.jp

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Anti-citrullinated peptide antibody (ACPA) is a highly specific serological marker for rheumatoid arthritis (RA).1,,3 Different HLA-DRB1 alleles have been shown to be associated with the susceptibility to ACPA-positive RA.4 5 Former studies demonstrated that HLA-DRB alleles carrying a shared epitope (SE),6 consisting of a conserved amino acid motif at positions 70–74 of the HLA-DRβ chain, were strongly associated with ACPA-positive RA and with higher ACPA levels in European and Japanese populations.7,,9 On the other hand, HLA-DRB1*09:01 was recently found to be negatively associated with ACPA levels in the Japanese.9 These observations imply that combinations of HLA-DRB1 alleles differentially influence ACPA levels in ACPA-positive RA.

To address this question, we conducted a genetic association study employing 2457 ACPA-positive Japanese RA patients. ACPA was quantified by MESACUP CCP ELISA kit (MBL Co Ltd, Nagoya, Japan) with a cut-off level of 4.5 U/ml. The patients were then divided into three groups …

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