Associated factors with cerebrospinal fluid cytokine levels in patients with neuropsychiatric systemic lupus erythematosus

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09901
• 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
• Principal Investigator: Takao Fujii 和歌山県立医科大学, 医学部, 教授 (70255462)
• Research Collaborator: Ishigooka Nozomi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 全身性エリテマトーデス / 抗核抗体 / サイトカイン / 中枢神経症状

Outline of Final Research Achievements

Autoantibodies (autoAbs) and inflammatory mediators (IMs) in cerebrospinal fluid (CSF) may be involved in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). We examined combined effects of CSF anti-N-methyl D-aspartate receptor NR2 subunit (NR2) Ab and anti-U1RNP Ab on IMs in patients with NPSLE. CSF samples were collected from 69 patients with acute-phase NPSLE and 13 non-NPSLE controls. Levels of IL-6, IL-8, and monokine induced by IFN-γ (MIG) in CSF were measured by quantitative multiplex cytokine analysis. Elevated CSF IL-6 and IL-8 levels were mainly associated with anti-NR2 and U1RNP Ab positivity, respectively. CSF IL-6, IL-8 and MIG levels were higher in CSF anti-NR2 and anti-U1RNP Ab double positive group than in anti-NR2 Ab-positive alone group. Therefore, CSF anti-NR2 and anti-U1RNP Abs have combined effects on the elevation of CSF IL-6 and MIG levels in patients with NPSLE.

Free Research Field

リウマチ・膠原病分野

Academic Significance and Societal Importance of the Research Achievements

膠原病の代表的疾患である全身性エリテマトーデスではしばしば脳の炎症を引き起こし、生命予後に影響を与える。この病態（NPSLE）は極めて重症と考えられ、そりよい治療法の開発が望まれるが、世界的にもガイドラインが整備されているとは言いがたい。本研究で、NPSLE患者の症状と深く関連するとされる脳脊髄液（CSF）中の液性因子がいかなる自己抗体と関連するかを明確にした。専門施設においてCSFは比較的容易に採取できるため、その自己抗体の検査を行うことでいかなる液性因子をターゲットとして治療すればよいかについて示唆に富む結果が得られたため、近日中に論文発表する予定である。