Analysis of the role of anti-citrullinated peptide antibody in RA pathogenesis to aim developing optimal treatment.

2020 Fiscal Year Annual Research Report

• Project/Area Number: 18K08411
• Research Institution: Nagasaki University
• Principal Investigator: 岩本 直樹 長崎大学, 医歯薬学総合研究科(医学系), 助教 (80437897)
• Co-Investigator(Kenkyū-buntansha): 増山 律子 長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (60297596) [Withdrawn] ; 玉井 慎美 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (60380862) ; 一瀬 邦弘 長崎大学, 医歯薬学総合研究科(医学系), 講師 (60437895) ; 川上 純 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90325639)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 破骨細胞 / 単球 / 抗CCP抗体 / M1単球 / 滑膜線維芽細胞 / ケモカイン

Outline of Annual Research Achievements

関節リウマチ患者末梢血よりビーズ法によりCD14陽性細胞を抽出し、RANKL含有培地にて抗CCP抗体存在下に破骨細胞への分化をおこない、抗CCP抗体誘導性破骨細胞と関節リウマチ患者背景について関連解析をおこなった。抗CCP抗体添加により破骨細胞形成数は増加しており、抗CCP抗体は関節リウマチ患者由来CD14陽性細胞においても破骨細胞分化促進作用を認めた。患者背景との比較では疾患活動性（DAS28-ESR）との相関は認めなかったものの生物製剤投与群において抗CCP抗体誘導性破骨細胞形成数が増加していた。また、M1・M2単球との解析ではM1単球（CD14＋CD68+CCR2+）/M2単球（CD14+CD163+CX3CR1＋)比が高い症例ほど破骨細胞分化形成数が高い傾向があった。
さらに、CTLA4-Igによる破骨細胞分化抑制は既知であるが、抗CCP抗体誘導性破骨細胞分化の過程においてCTLA4-Igを添加したところ破骨細胞分化の抑制を認め、抗CCP抗体陽性関節リウマチ患者でアバタセプト(CTLA4-Ig)がより有効性を発揮する1因である可能性が示唆された。
RA患者由来滑膜線維芽細胞（RASC）への抗CCP抗体の作用の解析では、抗CCP抗体刺激後にサイトカイン・ケモカイン産生ついてmultuplex bead assayにより38のサイトカイン・ケモカインを測定したところ、IL-6などの炎症性サイトカインの上昇は認めなかったが、
MCP-3の上昇を認めた。　また、RASCー骨芽細胞分化能への影響を検討したが、抗CCP抗体刺激の有無による骨芽細胞分化能の差異は認めなかった。

Research Products

• [Journal Article] Comparison of the quantitative measurement of 18F-FDG PET/CT and histopathological findings in IgG4-related disease. (2021)
  • Author(s): Tsuji S, Iwamoto N, Horai Y, Fujikawa K, Fujita Y, Fukui S, Ideguchi R, Michitsuji T, Nishihata S, Okamoto M, Tsuji Y, Endo Y, Shimizu T, Sumiyoshi R, Koga T, Kawashiri SY, Igawa T, Ichinose K, Tamai M, Nakamura H, Origuchi T, Kudo T, Kawakami A.
  • Journal Title: Clin Exp Rheumatol. Volume: epub Pages: epub
  • Peer Reviewed
• [Journal Article] Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis (2021)
  • Author(s): Endo Yushiro、Kawashiri Shin-ya、Morimoto Shimpei、Nishino Ayako、Okamoto Momoko、Tsuji Sosuke、Takatani Ayuko、Shimizu Toshimasa、Sumiyoshi Remi、Igawa Takashi、Koga Tomohiro、Iwamoto Naoki、
  • Journal Title: Medicine Volume: 100 Pages: e23254～e23254
  • DOI: 10.1097/MD.0000000000023254
  • Peer Reviewed
• [Journal Article] Life prognosis and renal relapse after induction therapy in Japanese patients with proliferative and pure membranous lupus nephritis. (2020)
  • Author(s): Okamoto M, Kitamura M, Sato S, Fujikawa K, Horai Y, Matsuoka N, Tsuboi M, Nonaka F, Shimizu T, Koga T, Kawashiri SY, Iwamoto N, Tamai M, Nakamura H, Origuchi T, Nishino T, Kawakami A, Ichinose K.
  • Journal Title: Rheumatology (Oxford). Volume: epub Pages: epub
  • Peer Reviewed
• [Journal Article] Effectiveness and safety of non-tumor necrosis factor inhibitor therapy for anti-human T-cell leukemia virus type 1 antibody-positive rheumatoid arthritis (2020)
  • Author(s): Endo Yushiro、Fukui Shoichi、Umekita Kunihiko、Suzuki Takahisa、Miyamoto Junya、Morimoto Shimpei、Shimizu Toshimasa、Koga Tomohiro、Kawashiri Shin-ya、Iwamoto Naoki、
  • Journal Title: Modern Rheumatology Volume: epub Pages: 1～12
  • Peer Reviewed
• [Journal Article] Next-generation sequencing of the whole MEFV gene in Japanese patients with familial Mediterranean fever: a case-control association study. (2020)
  • Author(s): Koga T, Sato S, Mishima H, Migita K, Endo Y, Umeda M, Sumiyoshi R, Nonaka F, Fukui S, Kawashiri SY, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Ueki Y, Masumoto J, Agematsu K, Yachie A, Yoshiura KI, Eguchi K, Kawakami A.
  • Journal Title: Clin Exp Rheumatol. Volume: 127 Pages: 35-41
  • Peer Reviewed
• [Journal Article] Rheumatoid arthritis patients with low baseline Health Assessment Questionnaire scores have a risk of functional disability progression: a post hoc analysis of a nationwide longitudinal cohort in Japan. (2020)
  • Author(s): Sumiyoshi R, Hidaka T, Koga T, Okada A, Fukuda T, Ishii T, Ueki Y, Kodera T, Nakashima M, Takahashi Y, Honda S, Horai Y, Watanabe R, Okuno H, Aramaki T, Izumiyama T, Takai O, Miyashita T, Kawashiri SY, Iwamoto N,
  • Journal Title: Clin Exp Rheumatol. Volume: 38 Pages: 1096-1101
  • Peer Reviewed
• [Journal Article] Reduction in the percentage of circulating variable delta 2T cells in systemic lupus erythematosus (2020)
  • Author(s): Koga Tomohiro、Endo Yushiro、Umeda Masataka、Sato Tomohito、Mizunoo Yuko、Furukawa Kaori、Shimizu Toshimasa、Sumiyoshi Remi、Kawashiri Shin-ya、Iwamoto Naoki、Igawa Takashi、Ichinose Kunihiro、Tamai Mami、Nakamura Hideki、Origuchi Tomoki、Kawakami Atsushi
  • Journal Title: Clinical Immunology Volume: 220 Pages: 108577～108577
  • DOI: 10.1016/j.clim.2020.108577
  • Peer Reviewed
• [Journal Article] Comparison of complete renal response and mortality in early- and late-onset lupus nephritis: a multicenter retrospective study of a Japanese cohort (2020)
  • Author(s): Ichinose Kunihiro、Kitamura Mineaki、Sato Shuntaro、Fujikawa Keita、Horai Yoshiro、Matsuoka Naoki、Tsuboi Masahiko、Nonaka Fumiaki、Shimizu Toshimasa、Sumiyoshi Remi、Koga Tomohiro、Kawashiri Shin-ya、Iwamoto Naoki、Igawa Takashi、Tamai Mami、Nakamura Hideki、Origuchi Tomoki、Nishino Tomoya、Kawakami Atsushi
  • Journal Title: Arthritis Research & Therapy Volume: 22 Pages: 175
  • DOI: 10.1186/s13075-020-02271-3
  • Peer Reviewed
• [Journal Article] Contributing factors of clinical outcomes at 1 year post-diagnosis in early rheumatoid arthritis patients with tightly controlled disease activity in clinical practice: a retrospective study (2020)
  • Author(s): Kawashiri Shin-ya、Endo Yushiro、Okamoto Momoko、Tsuji Sosuke、Shimizu Toshimasa、Sumiyoshi Remi、Koga Tomohiro、Iwamoto Naoki、Ichinose Kunihiro、Tamai Mami、Nakamura Hideki、Origuchi Tomoki、Kawakami Atsushi
  • Journal Title: Modern Rheumatology Volume: 31 Pages: 343～349
  • DOI: 10.1080/14397595.2020.1795392
  • Peer Reviewed
• [Journal Article] Comparison of lung microbiota between antineutrophil cytoplasmic antibody-associated vasculitis and sarcoidosis (2020)
  • Author(s): Fukui Shoichi、Morimoto Shimpei、Ichinose Kunihiro、Nakashima Shota、Ishimoto Hiroshi、Hara Atsuko、Kakugawa Tomoyuki、Sakamoto Noriho、Tsuji Yoshika、Aramaki Toshiyuki、Koga Tomohiro、Kawashiri Shin-ya、Iwamoto Naoki、
  • Journal Title: Scientific Reports Volume: 10 Pages: 9466
  • DOI: 10.1038/s41598-020-66178-4
  • Peer Reviewed
• [Journal Article] Anti-EJ Antibody-positive Anti-synthetase Syndrome Associated with Retroperitoneal Sarcoma (2020)
  • Author(s): Fukui Saeko、Kobayashi Kazuma、Fujita Yuya、Fukui Shoichi、Iwamoto Naoki、Adachi Tomohiko、Hidaka Masaaki、Takatsuki Mitsuhisa、Abe Kuniko、Kuwana Masataka、Kawakami Atsushi、Eguchi Susumu
  • Journal Title: Internal Medicine Volume: 59 Pages: 2071～2076
  • DOI: 10.2169/internalmedicine.3923-19
  • Peer Reviewed
• [Journal Article] Non-TNF inhibitor switchers versus TNF inhibitor cyclers from multicentre rheumatoid arthritis ultrasonography prospective cohort in Japan (2020)
  • Author(s): Endo Yushiro、Kawashiri Shin-ya、Morimoto Shimpei、Nishino Ayako、Okamoto Momoko、Tsuji Sosuke、Takatani Ayuko、Shimizu Toshimasa、Sumiyoshi Remi、Igawa Takashi、Koga Tomohiro、Iwamoto Naoki、
  • Journal Title: Immunological Medicine Volume: 43 Pages: 115～120
  • DOI: 10.1080/25785826.2020.1757920
  • Peer Reviewed
• [Journal Article] Interleukin-18 and fibroblast growth factor 2 in combination is a useful diagnostic biomarker to distinguish adult-onset Still’s disease from sepsis (2020)
  • Author(s): Koga Tomohiro、Sumiyoshi Remi、Furukawa Kaori、Sato Shuntaro、Migita Kiyoshi、Shimizu Toshimasa、Umeda Masataka、Endo Yushiro、Fukui Shoichi、Kawashiri Shin-ya、Iwamoto Naoki、Ichinose Kunihiro、Tamai Mami、Nakamura Hideki、Origuchi Tomoki、Nonaka Fumiaki、Yachie Akihiro、Kondo Hideaki、Maeda Takahiro、Kawakami Atsushi
  • Journal Title: Arthritis Research & Therapy Volume: 22 Pages: 108
  • DOI: 10.1186/s13075-020-02200-4
  • Peer Reviewed
• [Journal Article] Thymus and Activation-regulated Chemokine as a Biomarker for IgG4-related Disease (2020)
  • Author(s): Umeda Masataka、Origuchi Tomoki、Kawashiri Shin-ya、Koga Tomohiro、Ichinose Kunihiro、Furukawa Kaori、Sato Tomohito、Tsuji Sousuke、Endo Yushiro、Takatani Ayuko、Shimizu Toshimasa、Fukui Shoichi、Iwamoto Naoki、Igawa Takashi、Tamai Mami、Nakamura Hideki、Kawakami Atsushi
  • Journal Title: Scientific Reports Volume: 10 Pages: 6010
  • DOI: 10.1038/s41598-020-62941-9
  • Peer Reviewed
• [Journal Article] Differences in musculoskeletal ultrasound findings between RS3PE syndrome and elderly-onset rheumatoid arthritis (2020)
  • Author(s): Kawashiri Shin-ya、Suzuki Takahisa、Okada Akitomo、Tsuji Sousuke、Takatani Ayuko、Shimizu Toshimasa、Koga Tomohiro、Iwamoto Naoki、Ichinose Kunihiro、Nakamura Hideki、Origuchi Tomoki、Kawakami Atsushi
  • Journal Title: Clinical Rheumatology Volume: 39 Pages: 1981～1988
  • DOI: 10.1007/s10067-020-04931-w
  • Peer Reviewed
• [Journal Article] Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia) (2020)
  • Author(s): Sumita Yoshinori、Iwamoto Naoki、Seki Makoto、Yoshida Takako、Honma Ryo、Iwatake Mayumi、Ohba Seigo、Takashi I.、Hotokezaka Yuka、Harada Hiroshi、Kuroshima Shinichiro、Nagai Kazuhiro、Asahara Takayuki、Atsushi Kawakam I、Asahina Izumi
  • Journal Title: Medicine Volume: 99 Pages: e20788～e20788
  • DOI: 10.1097/MD.0000000000020788
  • Peer Reviewed
• [Presentation] 関節リウマチ患者におけるバリシチニブの有効性および安全性の検討 ～トファシチニブからの切り替え療法含めて～ (2020)
  • Author(s): 岩本直樹
  • Organizer: 日本リウマチ学会
• [Presentation] HR-pQCTを用いた関節リウマチ治療経過における関節構造変化の解析. (2020)
  • Author(s): 岩本直樹
  • Organizer: 日本リウマチ学会