Pathogenicity of anti-U1RNP antibodies in neuropsychiatric systemic lupus erythematous

• Project/Area Number: 25461472
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Wakayama Medical University (2015); Kyoto University (2013-2014)
• Principal Investigator: FUJII Takao 和歌山県立医科大学, 医学部, 教授 (70255462)
• Co-Investigator(Kenkyū-buntansha): HASHIMOTO Motomu 京都大学, 大学院医学研究科, 助教 (60512845)
• Research Collaborator: KONDO Seiko ; ISHIGOOKA Nozomi
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 全身性エリテマトーデス / 中枢神経障害 / 自己抗体 / サイトカイン / 抗核抗体 / 脳脊髄液 / ケモカイン / 中枢神経症状

Outline of Final Research Achievements

In patients with systemic lupus erythematosus (SLE), neuropsychiatric manifestations (NPSLE) is a refractory disorder, because their disease-specific markers and treatment strategy are not well determined. The present study shows a certain subset of NPSLE, which has a link of cerebrospinal fluid (CSF)-autoantibodies, CSF-inflammatory mediators, and blood brain barrier (BBB) permeabilities. Especially, CSF-IL-6 concentration was elevated in association with anti-NR2 antibodies by BBB injury. Also, anti-U1RNP antibodies may activate IFN-α production intrathecally and up-regulate CSF-IL-6 in the presence of CSF-anti-NR2 antibodies. We can conclude that both anti-NR2 and U1RNP antibody detections in NPSLE may be useful not only for diagnosis, but also treatment decision in primary NPSLE patients.

Research Products

• [Journal Article] Personal Authentication Analysis Using Finger-Vein Patterns in Patients with Connective Tissue Diseases―Possible Association with Vascular Disease and Seasonal Change - (2015)
  • Author(s): Kono M, Miura N, Fujii T, et al.
  • Journal Title: PLoS One Volume: 10 Issue: 12 Pages: e0144952-e0144952
  • DOI: 10.1371/journal.pone.0144952
  • NAID: 120005763405
  • Peer Reviewed / Open Access
• [Journal Article] Periodontitis and Porphyromonas gingivalis in Preclinical Stage of Arthritis Patients. (2015)
  • Author(s): Hashimoto M, Yamazaki T, Hamaguchi M, Morimoto T, Yamori M, Asai K, Isobe Y, Furu M, Ito H, Fujii T, et al.
  • Journal Title: PLoS One Volume: 10
  • NAID: 120005595898
  • Peer Reviewed / Open Access
• [Journal Article] Direct and Indirect Pathogenic Roles of Autoantibodies in Systemic Autoimmune Diseases (2014)
  • Author(s): Takao Fujii
  • Journal Title: Allergology International Volume: 63 Issue: 4 Pages: 515-522
  • DOI: 10.2332/allergolint.14-RAI-0801
  • NAID: 130004705231
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association between anti-U1 ribonucleoprotein antibodies and inflammatory mediators in cerebrospinal fluid of patients with neuropsychiatric systemic lupus erythematosus. (2014)
  • Author(s): Tomoko Yokoyama, Takao Fujii, Seiko Kondo-Ishikawa, Noriyuki Yamakawa, Masayoshi Nakano, Naoichiro Yukawa, Hajime Yoshifuji, Koichiro Ohmura, and Tsuneyo Mimori.
  • Journal Title: Lupus Volume: 23 Issue: 7 Pages: 635-642
  • DOI: 10.1177/0961203314522337
  • NAID: 120005458289
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Deficient leptin signaling ameliorates systemic lupus erythematosus lesions in MRL/Mp-Fas lpr mice (2014)
  • Author(s): Fujita Y, Fujii T, Mimori T, Sato T, Nakamura T, Iwao H, Nakajima A, Miki M, Sakai T, Kawanami T, Tanaka M, Masaki Y, Fukushima T, Okazaki T and Umehara H
  • Journal Title: Journal of immunology Volume: 192 Issue: 3 Pages: 979-984
  • DOI: 10.4049/jimmunol.1301685
  • Peer Reviewed
• [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] 膠原病診療における自己抗体測定の 臨床的意義と活用法 (2016)
  • Author(s): 藤井 隆夫
  • Organizer: 第60回日本リウマチ学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-04-21
• [Presentation] Neuropsychiatric SLEにおける血液脳関門の透過性と脳脊髄液中の炎症性メディエーターとの関係 (2016)
  • Author(s): 石郷岡 望, 藤井 隆夫, 近藤 聖子, 村上 孝作, 笹井 蘭, 橋本 求, 井村 嘉孝, 湯川 尚一郎, 吉藤 元, 田中 真生, 大村 浩一郎, 三森 経世
  • Organizer: 第60回日本リウマチ学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-04-21
• [Presentation] 精神神経ループスにおける脳脊髄液中の自己抗体とサイトカインとの相関 (2016)
  • Author(s): 近藤 聖子, 藤井 隆夫, 石郷岡 望, 橋本 求, 井村 嘉孝, 湯川 尚一郎, 吉藤 元, 大村 浩一郎, 三森 経世
  • Organizer: 第113回日本内科学会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-15
• [Presentation] 全身性エリテマトーデスの中枢神経障害における髄液中自己抗体測定の臨床的有用性とその限界について (2015)
  • Author(s): 藤井 隆夫、近藤 聖子、石郷岡 望、三森 経世
  • Organizer: 第43回日本臨床免疫学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2015-10-22
• [Presentation] Neuropsychiatric SLEにおける脳脊髄液中の抗NR2・抗U1RNP抗体とサイトカインとの関係 (2015)
  • Author(s): 近藤 聖子, 藤井 隆夫, 石郷岡 望, 村上 孝作, 橋本 求, 井村 嘉孝, 湯川 尚一郎, 吉藤 元, 大村 浩一郎, 三森 経世
  • Organizer: 第59回日本リウマチ学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-23
• [Presentation] Direct and indirect pathogenic roles of autoantibodies in neuropsychiatricsystemic lupus erythematosus. (2014)
  • Author(s): Takao Fujii
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
  • Invited
• [Presentation] 全身性自己免疫疾患における自己抗体の臨床的意義とその病原性について (2014)
  • Author(s): 藤井隆夫
  • Organizer: 第42回日本臨床免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-09-25 – 2014-09-27
  • Invited
• [Presentation] Neuropsychiatric SLE患者脳脊髄液中の抗NR2抗体と抗U1RNP抗体がIL-6に与える影響 (2014)
  • Author(s): 近藤聖子、藤井隆夫、石郷岡望、山川範之、橋本求、井村嘉孝、湯川尚一郎、吉藤元、大村浩一郎、三森経世
  • Organizer: 第42回日本臨床免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 自己抗体の基礎から臨床まで (2014)
  • Author(s): 藤井隆夫
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24 – 2014-04-26
  • Invited
• [Presentation] 全身性エリテマトーデスにおける中枢神経障害について (2014)
  • Author(s): 藤井隆夫
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24 – 2014-04-26
  • Invited
• [Presentation] 自己抗体の基礎から臨床まで
  • Author(s): 藤井 隆夫
  • Organizer: 日本リウマチ学会総会
  • Place of Presentation: 東京
  • Invited
• [Book] 内科学書 (2013)
  • Author(s): 藤井 隆夫
  • Total Pages: 4
  • Publisher: 中山書店
• [Remarks] 京都大学医学部附属病院リウマチセンター
  • URL: http://www.racenter.kuhp.kyoto-u.ac.jp/
• [Remarks] 京都大学医学部附属病院リウマチセンター
  • URL: http://www.racenter.kuhp.kyoto-u.ac.jp/