2022 Fiscal Year Final Research Report
Analysis of mechanism of antiphospholipid antibody-induced central nervous system impairment
Project/Area Number |
20H03718
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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Research Institution | Hokkaido University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
藤枝 雄一郎 北海道大学, 大学病院, 助教 (70790872)
奥 健志 北海道大学, 大学病院, 講師 (70544295)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 精神神経SLE / 抗リン脂質抗体(aPL) / 全身性エリテマトーデス / 認知機能障害 |
Outline of Final Research Achievements |
WBCAL-1, immunoglobulin G (IgG) isotype of mouse monoclonal anti-β2 glycoprotein I (GPI) antiphospholipid antibody was cerebroventricularly infused with the osmotic pump and was deposited in hippocampal CA 2-3 region. Although neuronal death was not observed using TUNEL staining, CD68-positive activated microglia were abundant around the CA 2-3 region. Bulk-RNA sequencing of the hippocampus revealed no difference of genes expressions between the WBCAL-1- and control IgG-infused groups, and specific expression of β2GPI in the CA2-3 region was not found using β2GPI-knock out mice. Further investigation will be needed to confirm the WBCAL-1 binding factor except β2GPI in the hippocampus, the pathogenesis of microglial activation and the effects on neuropsychiatric phenotype.
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Free Research Field |
膠原病・アレルギー内科学
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Academic Significance and Societal Importance of the Research Achievements |
神経症状は数ある膠原病の病変のなかでも重要で、免疫抑制療法は進歩しているが、中枢神経症状を発症し寛解導入できなかった患者は社会的制限を強いられる。本研究は、抗リン脂質抗体が中枢神経へどのように影響を与えるかを評価した。特に抗リン脂質抗体は海馬CA2-3領域の神経細胞に沈着し、機能へ直接影響を与える可能性、その結合にβ2GPIを介さない可能性、また同領域のミクログリア活性化が明らかとなった。局所的な神経機能変化や炎症が、若年者に重篤な後遺症をもたらしうる抗リン脂質抗体を介した神経病変に関わる可能性を示し、今後の研究、病態予防や治療の原石となるという点で社会的意義がある。
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