Analysis of the mechanism of blood-brain barrier damages in NPSLE
| Project/Area Number |
15K09556
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
永井 立夫 北里大学, 医学部, 講師 (60365947)
小川 英佑 北里大学, 医学部, 助教 (30525423)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | NPSLE / acute confusional state / MRI / IL-6 / anti-Sm / C5a / 脳血液関門 / 自己抗体 / 抗Sm抗体 / 単球 / 中枢神経ループス / 補体第５成分 / ループス腎炎 / 脳MRI |
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| Outline of Final Research Achievements |
Acute confusional state (ACS) is the most recalcitrant manifestation in diffuse neuropsychiatric systemic lupus erythematosus (NPSLE). We have disclosed that the presence of brain MRI abnormalities, the presence of serum anti-Sm antibodies and serum IL-6 levels significantly increased the risk for mortality in multivariate analysis in a retrospective study of 36 patients with ACS.
The damage of blood brain barrier (BBB) has been found to be important in the development of ACS. We have disclosed that serum C5a was elevated in NPSLE, contributing to BBB damages. We have also revealed that serum IL-6 might play a most important role in BBB breakdown in NPSLE. Moreover, we have demonstrated that serum anti-Sm antibodies play a most important role in the disruption of BBB. Finally, it was demonstrated that anti-Sm synergistically enhanced the production of IL-6 by human monocytes in the presence of anti-RNP, suggesting that anti-Sm might damage BBB through such an inflammatory process.
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Understanding the Antibody Repertoire in Neuropsychiatric Systemic Lupus Erythematosus and Neuromyelitis Optica Spectrum Disorder: Do They Share Common Targets?2018
Author(s)
Mader S, Jeganathan V, Arinuma Y, Fujieda Y, Dujmovic I, Drulovic J, Shimizu Y, Sakuma Y, Stern JNH, Aranow C, Mackay M, Yasuda S, Atsumi T, Hirohata S, Diamond B.
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Journal Title
Arthritis Rheumatology
Volume: 70
Issue: 2
Pages: 277-286
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease: Efficacy, safety, and pharmacokinetics in a multicenter, prospective, open-label, single-arm phase 3 study.2016
Author(s)
Hibi T, Hirohata S, Kikuchi H, Tateishi U, Sato N, Ozaki K, Kondo K, Ishigatsubo Y.
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Journal Title
Medicine (Baltimore)
Volume: 95
Issue: 24
Pages: e3863-e3863
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Upregulation of Complement C3 and Alpha-2-Macroglobulin in Cerebrospinal Fluid of Neuropsychiatric Systemic Lupus Erythematosus .2015
Author(s)
Asano T, Sato S, Kobayashi H, Kariya Y, Ito H, Hoshi K, Yoshihara A, Ugawa Y, Takahashi M, Sekine H, Hirohata S, Watanabe H, Ohira H, Hashimoto Y.
Organizer
79th Annual Scientific Meeting, American College of Rheumatology
Place of Presentation
San Francisco (U.S.A.)
Year and Date
2015-11-08
Related Report
Int'l Joint Research
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