Study on the relationship between arthritis and the quality of sleep

• Project/Area Number: 25515003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 睡眠科学
• Research Institution: Kyushu University
• Principal Investigator: Shiozawa Shunichi 九州大学, 大学病院, 学術研究員(特任教授) (40154166)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 関節リウマチ / 睡眠 / 生物学的製剤 / rheumatoid arthritis / sleep / biological DMARDs / 睡眠の質 / quality of sleep / 概日リズム / 疾患活動性 / 日常生活動作 / 睡眠障害 / メラトニン作動薬 / ラメルテオン

Outline of Final Research Achievements

The contribution of inflammation (arthritis) to the quality of sleep and vise versa was studied in the patients with rheumatoid arthritis (RA). We have studied 517 patients with rheumatoid arthritis with biologic DMARDs (tocilizmab 175, abatacept 98, or infliximab 144). Evaluation was made with Pittsburgh score, Epworth score and actigraphy, and the results were compared with arthritic indices. As a result, Pittsburgh score showed presence of sleep disturbance, in which global score showed 6.42±2.76 which was higher than normal level 5, thus indicating the presence of sleep disturbance. Actigraphy showed that %sleep 89.1±10.5, total wake after sleep 49.5±45.2 min, average wake after sleep onset 9.9±23.3times, and these values were abnormal as compared with healthy controls. Further, these values showed a posistive correlation with C-reactive protein levels and swollen joint counts of patients. After biologic DMARDs treatments (n=517), these abnormalities were all normalized.

Research Products

• [Journal Article] MMP-3 as a predictor for structural remission in RA patients treated with MTX monotherapy. (2016)
  • Author(s): Shiozawa K, Yamane T et al. Shiozawa S(Last author)
  • Journal Title: Arthritis Res Ther Volume: 18 Pages: 1-9
  • DOI: 10.1186/s13075-016-0948-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model. (2016)
  • Author(s): Kamide D et al. Shiozawa S (Last 2nd author)
  • Journal Title: Cancer Sci Volume: 107
  • DOI: 10.1111/cas.12914
  • Peer Reviewed / Open Access
• [Journal Article] The impact of c-Fos/Activator protein-1 inhibition on allogeneic pancreatic islet transplantation. (2015)
  • Author(s): Yoshida T, Yamashita K, Watanabe M, Koshizuka Y, Kuraya D, Ogura M, Asahi Y, Ono H, Emoto S, Mizukami T, Kobayashi N, Shibasaki S, Tomaru U, Kamachi H, Matsushita M, Shiozawa S, Hirono S, Todo S.
  • Journal Title: Am J Transpl Volume: 15(10) Pages: 2565-2575
  • DOI: 10.1111/ajt.13338
  • Peer Reviewed / Open Access
• [Journal Article] T-5224, a selective inhibitor of c-Fos activator protein-1, improves survival by inhibiting serum high mobility group box-1 in lethal lipopolysaccharide-induced acute kidney injury model. (2015)
  • Author(s): Ishida M et al. Shiozawa S (Last 2nd author)
  • Journal Title: J Intensive Care Volume: 3
  • DOI: 10.1186/s40560-015-0115-2
  • NAID: 120005693960
  • Peer Reviewed / Open Access
• [Journal Article] Anti-carbamylated protein antibodies in rheumatoid arthritis patients of Asian descent. (2015)
  • Author(s): Verheul MK et al. Shiozawa S (Last author)
  • Journal Title: Rheumatology Volume: 54 Pages: 1930-1932
  • DOI: 10.1093/rheumatology/kev250
  • Peer Reviewed / Open Access
• [Journal Article] The impact of c-Fos/Activator protein-1 inhibition on allogeneic pancreatic islet transplantation. (2015)
  • Author(s): Yoshida T, Yamashita K, Watanabe M, Koshizuka Y, Kuraya D, Ogura M, Asahi Y, Ono H, Emoto S, Mizukami T, Kobayashi N, Shibasaki S, Tomaru U, Kamachi H, Matsushita M, Shiozawa S, Hirono S, Todo S.
  • Journal Title: Am J Transplantation Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Anti-carbamylated protein antibodies in rheumatoid arthritis patients of Asian descent. (2015)
  • Author(s): Verheul MK, Shiozawa K, Levarht EWN, Huizinga TWJ, Toes REM, Trouw LA, Shiozawa S.
  • Journal Title: Rheumatology Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] In vivo cell transfer assay to detect autoreactive T cell subsets. (2014)
  • Author(s): Miyazaki Y, Shiozawa S.
  • Journal Title: Methods Mol Biol Volume: 1142 Pages: 49-53
  • DOI: 10.1007/978-1-4939-0404-4_6
  • Peer Reviewed / Open Access
• [Journal Article] Studies on the T cell receptor (TCR) revision of autoantibody-inducing CD4 T (aiCD4 T) cell. (2014)
  • Author(s): Shiozawa S, Uto K.
  • Journal Title: Methods Mol Biol Volume: 1142 Pages: 65-73
  • DOI: 10.1007/978-1-4939-0404-4_8
  • Peer Reviewed / Open Access
• [Journal Article] Induction of de novo autoimmune disease in normal mice upon repeated immunization with antigen. (2014)
  • Author(s): Tsumiyama K, Shiozawa S.
  • Journal Title: Methods Mol Biol Volume: 1142 Pages: 85-90
  • DOI: 10.1007/978-1-4939-0404-4_10
  • Peer Reviewed / Open Access
• [Journal Article] IFNgamma-producing effector CD8 T lymphocytes cause immune glomerular injury by recognizing antigen presented as immune complex on target tissue. (2013)
  • Author(s): Tsumiyama K, A. Hashiramoto, M. Takimoto, S. Tsuji-Kawahara, M. Miyazawa, and S. Shiozawa
  • Journal Title: J Immunol Volume: 191 Pages: 91-96
  • DOI: 10.4049/jimmunol.1203217
  • Peer Reviewed
• [Journal Article] Self-organized criticality theory and the expansion of PD-1 positive effector CD4 T cells: search for autoantibody-inducing CD4 T cells. (2013)
  • Author(s): Y. Miyazaki, K. Tsumiyama, T. Yamane, M. Ito, S. Shiozawa
  • Journal Title: Front Immunol Volume: 4 Pages: 87-87
  • DOI: 10.3389/fimmu.2013.00087
  • Peer Reviewed
• [Journal Article] EWS/ATF1 activates Fos and induces soft tissue sarcomas from neural crest-derived cells. (2013)
  • Author(s): Aoki H
  • Journal Title: The Journal of Clinical Investigation Volume: 155 Pages: 600-10
  • DOI: 10.1172/jci63572
  • Peer Reviewed
• [Journal Article] A merged presentation of clinical and radiographic data using probability plots in a clinical trial, the JESMR study. (2013)
  • Author(s): Kameda H, Kanbe K, Sato E, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Yamanaka H, Takeuchi T
  • Journal Title: Ann Rheum Dis Volume: 72 Pages: 310-2
  • DOI: 10.1136/annrheumdis-2012-201804
  • Peer Reviewed
• [Journal Article] Shorter disease duration in important for tocilizumab to achieve Boolean (2013)
  • Author(s): Kawasaki Y, Hashiramoto A, Okano T, Sakai Y, Yamane T, Shiozawa K, Shiozawa S, Hashiramoto A.
  • Journal Title: Mod Rheumatol Volume: 23 Pages: 192-197
  • DOI: 10.1007/s10165-012-0822-7
  • Peer Reviewed
• [Journal Article] TNF-alpha modulates expression of the circadian clock gene Per2 in rheumatoid synovial cells. (2013)
  • Author(s): Yoshida K, Hashiramoto A, Okano T, Yamane T, Shibanuma N, Shiozawa S.
  • Journal Title: Scand J Rheumatol Volume: 42 Pages: 276-280
  • DOI: 10.3109/03009742.2013.765031
  • Peer Reviewed
• [Journal Article] Mixed connective tissue disease (MCTD) is distinct from SLE: study of MICA and HLA gene (2013)
  • Author(s): Yoshida K, Inoue H, Komai K, Yamane T, Hashiramoto A, Shiozawa K, Shiozawa S.
  • Journal Title: Tissue Antigens Volume: 81 Pages: 44-45
  • DOI: 10.1111/tan.12027
  • Peer Reviewed
• [Presentation] Endosome-to-cytoplasm pathway via Sec61 and proteasomal degradation as an essential component of antigen cross-presentation and the lupus tissue injury in systemic lupus erythematosus (SLE): Extension of our self-organized criticality theory. (2016)
  • Author(s): Tsumiyama K, Shiozawa S
  • Organizer: The American Association of Immunologist, 103rd annual meeting,
  • Place of Presentation: Seattle, Washington, USA
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] Specifying the autoantibody-inducing CD4 T cell (aiCD4 T cell) causing systemic lupus erythematosus (SLE) out of PD-1+CD45RBlo122lo CD4 subpopulation using mass spectrometry. (2015)
  • Author(s): Shiozawa S, Miyazaki Y, Tsumiyama K.
  • Organizer: Immunology 2015 (102th Annual Meeting of AAIS)
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2015-05-08 – 2015-05-12
• [Presentation] Specifying the autoantibody-inducing CD4 T cell causing systemic lupus erythematosus out of PD-1+CD45RBlo122lo CD4 subpopulation using mass spectrometry. (2015)
  • Author(s): Shiozawa S, Miyazaki Y, Tsumiyama K.
  • Organizer: The American Association of Immunologist, 102nd annual meeting,
  • Place of Presentation: New Orleans, Louisiana, USA
  • Year and Date: 2015-05-08
  • Int'l Joint Research
• [Presentation] Increase of endosomal Sec61 enhances antigen cross-presentation and induces immune glomerular injury: a novel ‘self-organized criticality theory’ explaining the cause of systemic lupus erythematosus. (2015)
  • Author(s): Tsumiyama K, Shiozawa S.
  • Organizer: The American Association of Immunologist, 102nd annual meeting,
  • Place of Presentation: New Orleans, Louisiana, USA
  • Year and Date: 2015-05-08
  • Int'l Joint Research
• [Presentation] The autoantibody-inducing CD4 T cell (aiCD4 T cell) causing SLE belongs to PD-1+CD45RBlo122lo CD4 subpopulation. (2014)
  • Author(s): Miyazaki Y, Tsumiyama K, Shiozawa S.
  • Organizer: Immunology 2014 (101th Annual Meeting of AAIS)
  • Place of Presentation: Pittsburgh, USA
  • Year and Date: 2014-05-02 – 2014-05-06
• [Presentation] Sec 61 plays an essential role in facilitating antigen cross-presentation. (2014)
  • Author(s): Tsumiyama K, Shiozawa S.
  • Organizer: Immunology 2014 (101th Annual Meeting of AAIS)
  • Place of Presentation: Pittsburg, USA
  • Year and Date: 2014-05-02 – 2014-05-06
• [Presentation] The autoantibody-inducing CD4 T cell (aiCD4 T cell) causing systemic lupus erythematosus (SLE) belongs to PD-1+CD45RBlo122lo CD4 subpopulation. (2014)
  • Author(s): Miyazaki Y, Tsumiyama K, Shiozawa S.
  • Organizer: The 101st Annual Meeting of American Association of Immunologists
  • Place of Presentation: Pittsburgh, USA
• [Presentation] Sec61 plays an essential role in facilitating antigen cross-presentation (2014)
  • Author(s): Tsumiyama K, Shiozawa S.
  • Organizer: The 101st Annual Meeting of American Association of Immunologists
  • Place of Presentation: Pittsburgh, USA
• [Presentation] Self-organized criticality theory in the pathogenesis of SLE. (2014)
  • Author(s): Shiozawa S
  • Organizer: Symposium on Human Papilloma Vaccines.
  • Place of Presentation: Tokyo, Japan
  • Invited
• [Presentation] Anti-carbamylated protein antibody in Japanese patients with rheumatoid arthritis. (2013)
  • Author(s): Shiozawa S, Trouw LA, Shiozawa K.
  • Organizer: ACR/ARHP Annual Meeting 13
  • Place of Presentation: San Diego, USA
• [Presentation] MMP3 as a predictor identifying a subgroup of rheumatoid patients who are successfully treated with methotrexate (MTX) alone but still subject to radiographic progression. (2013)
  • Author(s): Shiozawa S, Tanaka Y, Yoshihara R, Murata M, Yamane T, Tanaka C, Yo N, Shiozawa K.
  • Organizer: ACR/ARHP Annual Meeting 13
  • Place of Presentation: San Diego, USA
• [Presentation] PD-1+CD45RBlo 122lo autoantibody-inducing CD4 T cell (aiCD4 T cell) as a key in the pathogenesis of systemic lupus erythematosus. (2013)
  • Author(s): Miyazaki Y, Tsumiyama K, Shiozawa S.
  • Organizer: ACR/ARHP Annual Meeting 13
  • Place of Presentation: San Diego, USA
• [Book] 膠原病学、改訂第６版 (2015)
  • Author(s): 塩沢俊一著（単著）
  • Total Pages: 688
  • Publisher: 丸善
• [Book] 膠原病学 第6版 (2015)
  • Author(s): 塩沢俊一
  • Total Pages: 620
  • Publisher: 丸善
• [Book] Methods in Molecular Biology vol 1142 (2014)
  • Author(s): Shiozawa S, eds.
  • Total Pages: 204
  • Publisher: Springer Humana Press
• [Book] Arthritis Research: Methods in Molecular Biology Vol.1142 (2014)
  • Author(s): Shiozawa S, eds
  • Total Pages: 204
  • Publisher: Springer Humana Press
• [Book] 膠原病学 (2013)
  • Author(s): 塩沢俊一著
  • Total Pages: 660
  • Publisher: 丸善出版
• [Book] 器官病理学 (2013)
  • Author(s): 塩沢俊一（分担執筆）
  • Total Pages: 1018
  • Publisher: 南山堂
• [Book] 永井書店 (2013)
  • Author(s): 塩沢俊一他編
  • Total Pages: 269
  • Publisher: リウマチ病セミナー
• [Remarks] 九州大学病院共同研究部門リウマチ膠原病内科ホームページ
  • URL: http://www.rheumatology.beppu.hosp.kyushu-u.ac.jp