JP2018534910A - 免疫細胞、特にcd56+ nk細胞の同定のためのエピジェネティックマーカーとしてのmvd - Google Patents
免疫細胞、特にcd56+ nk細胞の同定のためのエピジェネティックマーカーとしてのmvd Download PDFInfo
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Abstract
Description
バイオマーカー比=a/b
a=Σ(C及び/又はmC及び/又はhmC及び/又はfC及び/又はcC)
b=Σ(C及び/又はmC及び/又はhmC及び/又はfC及び/又はcC)
として定義することができ、これにより、a及びbは1種〜4種の修飾によりそれぞれが異なる。新規のDNA修飾の発見では、この列挙が拡大されるだろう。
CD56+ NK細胞を同定するために、以下の配列(AMP2674、配列番号1)によるヒトゲノム領域に由来するバイサルファイト変換型サンプルにqPCRを行った。関連するCpGを灰色で網掛け処理している。
BLC25=Bリンパ球
CTL01=CD8+細胞傷害性T細胞
GRC52=顆粒球
MOC26=CD14+単球
NKC=CD56+NK細胞
NKT=CD56+CD3+NKT細胞
THC14=CD4+ヘルパーT細胞
TpG特異的(配列番号2):
Claims (15)
- サンプルにおいてCD56+ NK細胞を同定する方法であって、該方法が、メバロン酸(ジホスホ)デカルボキシラーゼ(MVD)に対する哺乳動物の遺伝子領域における少なくとも1つのCpG位置のメチル化状態を分析することを含み、好ましくは、分析される該遺伝子領域が、配列番号1による単位複製配列に位置しており、非CD56+ NK細胞と比較した場合の該遺伝子領域の脱メチル化又はメチル化の欠失がCD56+NK細胞の指標となる、方法。
- 前記少なくとも1つのCpG位置が、分析する前記遺伝子領域内の転写開始部位、プロモーター領域、5'又は3'非翻訳領域、エクソン、イントロン、エクソン/イントロン境界より上流の5'領域、及び/又は転写停止部位より下流の3'領域に存在する、請求項1に記載の方法。
- 前記少なくとも1つのCpG位置が、配列番号1による単位複製配列におけるCpG位置1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、及び20から選択されるCpGから選択され、又は、配列番号2若しくは配列番号3によるバイサルファイト変換される配列による単位複製配列2674番のフラグメントにおけるCpG位置10、11、12、及び13から選択される、請求項1又は2に記載の方法。
- バイサルファイト転換性の分析がメチル化特異性酵素消化、バイサルファイトシークエンシングから選択される方法、プロモーターメチル化、CpGアイランドメチル化、MSP、HeavyMethyl、MethyLight、Ms-SNuPEから選択される分析、及び増幅DNAの検出に基づく他の方法を含む、請求項1〜3のいずれか一項に記載の方法。
- CD56+ NK細胞の相対量を、分析する領域におけるメチル化頻度の相対量と、GAPDHによって例示される対照遺伝子におけるメチル化頻度の相対量との比較に基づいて定量することを更に含む、請求項1〜4のいずれか一項に記載の方法。
- 前記サンプルがヒト血液サンプルを含む哺乳動物の体液、又は組織、器官若しくは細胞型の血液サンプル、血中リンパ球のサンプル若しくはその画分から選択される、請求項1〜5のいずれか一項に記載の方法。
- 前記CD56+ NK細胞と、濾胞性ヘルパーT細胞、B細胞、細胞傷害性T細胞、顆粒球、単球、CD56++(bright)NK細胞、及びヘルパーT細胞、並びに任意にNKT細胞から選択される細胞型の全て又は少なくとも1つとを区別することを更に含む、請求項1〜6のいずれか一項に記載の方法。
- 同定する前記細胞を、全血及び/又は非トリプシン処理組織を使用して精製及び/又は富化する工程なしに行われる、請求項1〜7のいずれか一項に記載の方法。
- 同定される前記CD56+ NK細胞に基づいて前記哺乳動物の免疫状態を決定する工程を更に含む、請求項1〜8のいずれか一項に記載の方法。
- 哺乳動物においてCD56+ NK細胞のレベルをモニタリングする方法であって、請求項5〜9のいずれか一項に記載の方法を行うことと、さらに、同定された前記細胞の相対量を、同じ哺乳動物から先に又は並行して採取したサンプル及び/又は対照サンプルと比較することとを含む、方法。
- 前記哺乳動物に与える化学物質及び/又は生物学的物質に応じて前記CD56+ NK細胞の量を測定及び/又はモニタリングすることを更に含む、請求項1〜10のいずれか一項に記載の方法。
- 前記哺乳動物が自己免疫疾患、移植片拒絶反応、感染性疾患、癌及び/又はアレルギーを患っているか、又はそれらを患う可能性がある、請求項1〜11のいずれか一項に記載の方法。
- 哺乳動物においてCD56+ NK細胞を、MVDの遺伝子領域のCpG位置のバイサルファイト接近性の分析に基づいて同定、定量及び/又はモニタリングするキットであって、請求項1〜12のいずれか一項に記載の方法の実行用の成分を含む、又は、a)バイサルファイト試薬、及びb)配列番号1による領域のCpG位置から選択されるCpG位置のメチル化状態の分析用の材料、配列番号4〜配列番号11による配列から選択されるオリゴマーを含む、キット。
- 配列番号4〜配列番号11のいずれかによるオリゴマー、又は配列番号1、配列番号2又は配列番号3による単位複製配列。
- 哺乳動物におけるCD56+ NK細胞の同定、定量及び/又はモニタリングへの請求項13に記載のキット、又は請求項14に記載のオリゴマー若しくは単位複製配列の使用。
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GBGB1516971.7A GB201516971D0 (en) | 2015-09-25 | 2015-09-25 | MVD as epigenetic marker for the identification of immune cells, in particular CD56+ NK cells |
GB1516971.7 | 2015-09-25 | ||
PCT/EP2016/072522 WO2017050882A1 (en) | 2015-09-25 | 2016-09-22 | Mvd as epigenetic marker for the identification of immune cells, in particular cd56+ nk cells |
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DE102017125013B4 (de) * | 2017-10-25 | 2019-10-17 | Epiontis Gmbh | MCC als epigenetischer Marker zur Identifizierung von Immunzellen, insbesondere basophiler Granulozyten |
DE102018116353B4 (de) * | 2018-07-05 | 2020-06-10 | Epiontis Gmbh | Verfahren zum Nachweis und zur Zählung epigenetischer Immunzellen in humanen Blutproben für Immundiagnostik und Neugeborenen-Screening |
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USH2220H1 (en) * | 2001-08-10 | 2008-07-01 | Snp Consortium | Identification and mapping of single nucleotide polymorphisms in the human genome |
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EP2878680B1 (en) * | 2008-07-09 | 2016-06-08 | Celera Corporation | Genetic polymorphisms associated with cardiovascular diseases, methods of detection and uses thereof |
PL2248913T3 (pl) | 2009-04-28 | 2017-04-28 | Epiontis Gmbh | GNLY jako marker epigenetyczny do identyfikacji komórek naturalnej cytotoksyczności ekspresjonujących CD56 |
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GB201112586D0 (en) | 2011-07-22 | 2011-09-07 | Epiontis Gmbh | Epigenetic marker for the identification of natural killer cells |
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2015
- 2015-09-25 GB GBGB1516971.7A patent/GB201516971D0/en not_active Ceased
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2016
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US11788141B2 (en) | 2023-10-17 |
CN108026577B (zh) | 2022-09-23 |
EP3353321A1 (en) | 2018-08-01 |
EP3353321B1 (en) | 2020-11-04 |
WO2017050882A1 (en) | 2017-03-30 |
CA2995350A1 (en) | 2017-03-30 |
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HK1257705A1 (zh) | 2019-10-25 |
CN108026577A (zh) | 2018-05-11 |
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