JP2019128317A - 多発性硬化症の診断マーカー又は診断キット - Google Patents
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Abstract
Description
SJL/Jマウス(雌性,10週齢)に、Proteolipid proteinの139-151番目のアミノ酸配列(配列番号6:HCLGKWLGHPDKF,His Cys Leu GlyLys Trp Leu Gly His Pro Asp Lys Phe)に該当するペプチド(PLP139-151)を、完全フロイントアジュバントと共に免疫し、EAEを誘導した。なお、実験的アレルギー性脳脊髄炎(EAE:Experimental autoimmune encephalomyelitis)は、中枢神経組織由来の蛋白質抗原やペプチドを免疫することによって誘導される自己免疫モデルである。多発性硬化症(MS)と多くの病態を共有することから、MSの病態研究、治療法開発において使用されている。定法に従い、臨床症状を6段階で毎日評価した。
acute-EAEマウス脳から、クリオスタットで10 μm厚の新鮮凍結切片を作製した。組織切片を、エタノール、カルノア液で洗浄後、マトリックスとしてシナピン酸を噴霧した。質量分析装置は、UltrafleXtreme(Bruker Daltonics)を用いた。UltrafleXtremeは、最高性能のMALDI-TOF&TOF/TOFシステムであり、TOF/TOFモードで2 kHzの解析が可能である。データ解析は、fleximaging(Bruker Daltonics)ソフトウェアを用いて、EAEマウス組織に特異的なm/z 値を検索し、描出した。
新鮮凍結切片を4%パラホルムアルデヒド含有リン酸緩衝生理食塩水にて固定を行った。0.3%過酸化水素含有メタノールで内在性Peroxidaseを不活性化後、10%ヤギ血清でブロッキングを行った。一次抗体として、抗S100A9抗体、二次抗体として、ビオチン標識抗ラットIgG抗体を用いた。アビジン-ビオチン複合体を形成させ、3,3’-diaminobenzidine(DAB)法により検出を行った。
図2は、controlマウスとacute-EAEマウスとにおいて脳切片のIMS法による解析結果を示す図であり、そのうち(a)はcontrolであり、(b)はpre-EAEマウス脳であり、(c)はacute-EAEマウス脳であり、(d)はchronic-EAEマウス脳である。UltrafleXtreme(Bruker Daltonics)を用いた質量分析による結果、IMSにより、EAEマウス脳に特異的に検出されるm/z 12,971は、acute-EAEマウス脳のみならず、chronic-EAEマウス脳においても、更には、pre-EAEマウス脳においても認められた。
SJL/Jマウス(雌性,10週齢)にペプチド(PLP139-151)を完全フロイントアジュバントと共に免疫し、EAEを誘導したEAEマウスに、ペプチド免疫後、S100A9タンパク質の特異的阻害剤としてタスキニモドを2日に1回、経口投与した。Controlにはタスキニモドを投与しなかった。
配列番号6:ペプチド
Claims (3)
- S100A9タンパク質であることを特徴とする、多発性硬化症の検出又は発症予測のための診断マーカー。
- 検体から単離された生物学的試料から、多発性硬化症を検出又は発症予測するための診断キットであって、
S100A9タンパク質に対する特異的結合物質又はS100A9を増幅するプライマーセットを備える、多発性硬化症の検出又は発症予測のための診断キット。 - 前記生物学的試料が被検者の血液、血清、血漿、脳脊髄液、尿又は唾液である請求項2記載の多発性硬化症の検出又は発症予測のための診断キット。
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Citations (4)
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WO2006122723A1 (en) * | 2005-05-19 | 2006-11-23 | Vaecgene Biotech Gmbh | Method for the prevention and/or treatment of autoimmune disease or allogeneic transplant rejections |
WO2014208645A1 (ja) * | 2013-06-28 | 2014-12-31 | 中外製薬株式会社 | そう痒を伴う疾患に罹患した患者のil-31アンタゴニストによる治療に対する応答を予測する方法 |
JP2015533485A (ja) * | 2012-09-10 | 2015-11-26 | ヴェストファーリッシュ ヴィルヘルム−ユニバーシテート ミュンスター | 炎症性状態の予防、処置、および診断のための方法および化合物 |
WO2016198649A1 (en) * | 2015-06-12 | 2016-12-15 | Oryzon Genomics, S.A. | Biomarkers associated with lsd1 inhibitors and uses thereof |
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WO2006122723A1 (en) * | 2005-05-19 | 2006-11-23 | Vaecgene Biotech Gmbh | Method for the prevention and/or treatment of autoimmune disease or allogeneic transplant rejections |
JP2015533485A (ja) * | 2012-09-10 | 2015-11-26 | ヴェストファーリッシュ ヴィルヘルム−ユニバーシテート ミュンスター | 炎症性状態の予防、処置、および診断のための方法および化合物 |
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