Search for specific antibodies of anti-CCP antibody-negative rheumatoid arthritis -focusing on anti-carbamylated protein antibody-

• Project/Area Number: 26460649
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kyoto University
• Principal Investigator: OHMURA Koichiro 京都大学, 医学研究科, 准教授 (40432372)
• Research Collaborator: NAKABO Shuichiro
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 抗カルバミル化蛋白抗体 / 関節リウマチ / 対応抗原 / アルブミン / ミエロペルオキシダーゼ / 自己抗体 / カルバミル化 / 抗CarP抗体 / アルファスクリーン法 / 蛋白アレイ

Outline of Final Research Achievements

We found one of the target antigens of anti-carbamylated protein (CarP) antibody is carbamylated albumin (CarALB). Sensitivities of anti-CarALB antibody for anti-CCP antibody-positive rheumatoid arthritis (RA) and anti-CCP-negative RA are 44.6% and 18.3%, respectively (3.6% for healthy donors). Both Anti-CarP and anti-CarALB antibodies were positive in ~10-30% of other rheumatic diseases or collagen vascular diseases. We measured serum concentration of myeloperoxidase (MPO), which is the key enzyme of carbamylation in vivo, and found that MPO was higher in anti-CarALB-positive RA patients than in anti-CarALB-negative patients.

Research Products

• [Journal Article] Carbamylated albumin is one of the target antigens of anti-carbamylated protein antibodies. (2017)
  • Author(s): Nakabo S, Hashimoto M, Ito S, Furu M, Ito H, Fujii T, Yoshifuji H, Imura Y, Nakashima R, Murakami K, Kuramoto N, Tanaka M, Satoh J, Ishigami A, Morita S, Mimori T, Ohmura K.
  • Journal Title: Rheumatology (Oxford) Volume: in press Issue: 7 Pages: 1217-1226
  • DOI: 10.1093/rheumatology/kex088
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Significant association of periodontal disease with anti-citrullinated peptide antibody in a Japanese healthy population-the Nagahama study. (2015)
  • Author(s): C Terao, K Asai; M Hashimoto; T Yamazaki; K Ohmura; A Yamaguchi; K Takahashi; N Takei; T Ishii; T Kawaguchi; Y Tabara; M Takahashi; T Nakayama; S Kosugi; A Sekine; T Fujii; R Yamada; T Mimori; F Matsuda; K Bessho, Nagahama Study Group.
  • Journal Title: Journal of Autoimmunity Volume: 59 Pages: 85-90
  • DOI: 10.1016/j.jaut.2015.03.002
  • NAID: 120005601013
  • Peer Reviewed / Open Access
• [Journal Article] Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of genome-wide association study in a Japanese population. (2015)
  • Author(s): Terao C, Ohmura K, Kochi Y, Ikari K, Okada Y, Shimizu M, , Kubo M, Yamada R, Taniguchi A, Yamanaka H, Momohara S, Yamamoto K, Mimori T, Matsuda F.
  • Journal Title: Arthritis Res Ther Volume: 17 Issue: 1 Pages: 104-104
  • DOI: 10.1186/s13075-015-0623-4
  • NAID: 120005749954
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Rheumatoid Factor Is Associated With the Distribution of Hand Joint Destruction in Rheumatoid Arthritis. (2015)
  • Author(s): Terao C, Yamakawa N, Yano K, Markusse IM, Ikari K, Yoshida S, Furu M, Hashimoto M, Ito H, Fujii T, Ohmura K, Murakami K, Takahashi M, Hamaguchi M, Tabara Y, Taniguchi A, Momohara S, Raychaudhuri S, Allaart CF, Yamanaka H, Mimori T, Matsuda F.
  • Journal Title: Arthritis Rheumatol. Volume: 67 Issue: 12 Pages: 3113-3123
  • DOI: 10.1002/art.39306
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genetics of rheumatoid arthritis contributes to biology and drug discovery. (2014)
  • Author(s): Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Yoshida S, Graham RR, Manoharan A, Ortmann W, Bhangale T, Denny JC, （省略）, GARNET consortium, （以下省略）.
  • Journal Title: Nature Volume: 506 Issue: 7488 Pages: 376-381
  • DOI: 10.1038/nature12873
  • Peer Reviewed / Open Access
• [Journal Article] Inverse association between air pressure and rheumatoid arthritis synovitis: an observational study (2014)
  • Author(s): Terao C, Hashimoto M, Furu M, Nakabo S, Ohmura K, Nakashima R, Imura Y, Yukawa N, Yoshifuji H, Matsuda F, Ito H, Fujii T, Mimori T.
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: e85376-e85376
  • DOI: 10.1371/journal.pone.0085376
  • Peer Reviewed / Open Access
• [Journal Article] A Clinical, Pathological, and Genetic Characterization of Methotrexate-associated Lymphoproliferative Disorders (2014)
  • Author(s): Yamakawa N, Fujimoto M, Kawabata D, Terao C, Nishikori M, Nakashima R, Imura Y, Yukawa N, Yoshifuji H, Ohmura K, Fujii T, Kitano T, Kondo T, Yurugi K, Miura Y, Maekawa T, Saji H, Takaori-Kondo A, Matsuda F, Haga H, Mimori T
  • Journal Title: J Rheumatol Volume: 41 Pages: 293-299
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Significant association between CYP3A5 polymorphism and blood concentration of tacrolimus in patients with connective tissue diseases (2014)
  • Author(s): Tanaka K, Terao C, Ohmura K, Takahashi M, Nakashima R, Imura Y, Yoshifuji H, Yukawa N, Usui T, Fujii T, Mimori T, Matsuda F
  • Journal Title: J Hum Genet Volume: 59 Issue: 2 Pages: 107-109
  • DOI: 10.1038/jhg.2013.129
  • NAID: 120005587802
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serum milk fat globule epidermal growth factor 8 elevation may subdivide systemic lupus erythematosus into two pathophysiologically distinct subsets (2014)
  • Author(s): Yamamoto, N., Yamaguchi, H., Ohmura, K., Yokoyama, T., Yoshifuji, H., Yukawa, N., Kawabata, D., Fujii, T., Morita, S., Nagata, S. and Mimori, T.
  • Journal Title: Lupus Volume: 23 Issue: 4 Pages: 386-394
  • DOI: 10.1177/0961203314523870
  • Peer Reviewed / Open Access
• [Presentation] 無細胞タンパク質合成系を用いたハイスループットタンパク合成とAlphaScreenを組み合わせた、関節リウマチにおける新規自己抗体の網羅的検索 (2017)
  • Author(s): 中坊周一郎、大村浩一郎、三森経世
  • Organizer: 第61回日本リウマチ学会
  • Place of Presentation: 博多
  • Year and Date: 2017-04-22
• [Presentation] Carbamylated Human Albumin Is One of the Target Antigens of Anti-Carbamylated Protein Antibodies (2015)
  • Author(s): Shuichiro Nakabo, Koichiro Ohmura, Kosaku Murakami, Ran Nakashima, Moritoshi Furu, Masahiro Ishikawa, Motomu Hashimoto, Yoshitaka Imura, Naoichiro Yukawa, Hajime Yoshifuji, Hiromu Ito, Takao Fujii and Tsuneyo Mimori,
  • Organizer: American college of rheumatology annual meeting 2015
  • Place of Presentation: San Francisco
  • Year and Date: 2015-11-10
  • Int'l Joint Research
• [Presentation] Association of a Single Nucleotide Polymorphism (SNP) in IL-12B Region with Clinical Features and Peripheral T Cell Profiles of Patients with Takayasu Arteritis (2014)
  • Author(s): Yoshifuji H, Ohmura K, Mimori T,
  • Organizer: American college of rheumatology 2014,
  • Place of Presentation: Boston (USA)
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] 歯周病菌Red complexの存在は関節リウマチの治療抵抗性と相関する。 (2014)
  • Author(s): 橋本求、大村浩一郎、三森経世
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京（品川）
  • Year and Date: 2014-04-24 – 2014-04-26