JP2021502061A - 免疫細胞、特にpd1+ 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pdcd1 - Google Patents
免疫細胞、特にpd1+ 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pdcd1 Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6881—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/154—Methylation markers
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Analytical Chemistry (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Description
バイオマーカー比率=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)
(式中、a及びbは、1〜4種類の修飾でそれぞれ異なる。新規のDNA修飾の発見によりこの列挙は拡張され得る)。
PD1+ 細胞を同定するために、qPCRは、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(図3を参照されたい)、特にAMP 1876、AMP 1877、AMP 1878及びAMP 1879の領域(下線)で行われた。
1877プライマー(qPCR30 FW_T) - GTTTAGATTAGATTTGGTATTTTTGATT(配列番号6)
qPCR30_RV_T - CAAATCCTCTAAAAACAAACTCA(配列番号7)
qPCR30 Probe _T and C: - TCCCAACACAACCCATAAAACAATTTC(配列番号8)
qPCR30_FW_C - AGATTAGATTCGGTATTTTTGATCG(配列番号9)
qPCR30_RV_C - CAAATCCTCTAAAAACAAACTCG(配列番号10)
qPCR30_P _ C - CCCAACACAACCCGTAAAACGATTTC(配列番号11)
TTaggtTTtTtagggaTaagTtTgTtgtTTtTatTTTagTaTagTTTgtgggaTggtttTTttgtTTTtaatgggaTTaTggtTagagatgTTgggtTtggtTtgggTTagTaggttTTtTTgTTTggggTaggTagTTttTttTtgtgTgTttTtggaaagTaatgtTTtgtaatgTggtTtTtTtgTgggagTaTTTTTaTTgTTaTTtTaTaggTTtgttTTaTagTTTTgggatgggTtTtgtTtTTTtTTtgaTTTtgT
TTaggtTTtTtagggaTaagTtCgTtgtTTtTatTTTagTaTagTTCgtgggaCggtttTTttgtTTTtaatgggaTTaCggtTagagatgTCgggtTtggtTtgggTTagTaggttTTtTCgTTCggggTaggTagTTttTttTtgtgCgTttTtggaaagTaatgtTTtgtaatgCggtTtTtTtgCgggagTaTTTTTaTCgTTaTTtTaTaggTTtgttTTaTagTTTCgggatgggTtTtgtTtTTTtTTtgaTTTtgT
B cells B細胞
CD8 T cells CD8 T細胞
Granulocytes 顆粒球
Monocytes 単球
NK cells NK細胞
NK T cells NKT細胞
PD1+ TFH cells PD1+ TFH細胞
CD4+ TH cells CD4+ TH細胞
図2
Intended Methylation 所望のメチル化
Measured Methylation 測定されたメチル化
図4
protein coding タンパク質コーディング
nonsense mediated decay ナンセンス変異依存分解機構
Claims (15)
- サンプルにおいてPD1+ 細胞を同定する方法であって、該方法が、プログラム細胞死1(PDCD1)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又はプログラム細胞死1(PDCD1)に対する哺乳動物の配列番号1に記載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であり、非PD1+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PD1+ 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の転写開始、プロモーター領域、5'又は3'非翻訳領域、エキソン、イントロン、エキソン/イントロン境界よりも上流の5'領域に存在する、及び/又は解析される前記遺伝子領域の転写停止よりも下流の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2による単位複製配列(アンプリコン)1876番のCpG位置27、47、82、136、194、197、249、285、290、303、336、354及び369、配列番号3による単位複製配列1877番のCpG位置31、60、75、86、114、138、142、171、184、210、217及び241、配列番号4による単位複製配列1878番のCpG位置35、56、74、104、118、130、150、182、196及び212から選択されるCpGから選択され、又は、配列番号3による単位複製配列1877番のフラグメントにおけるCpG位置60、75、86、114、138、142、171、184、210、217及び241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。
- PD1+ 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又は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PD1+ 細胞と、PD1濾胞細胞、細胞傷害性T細胞、顆粒球、単球、B細胞、CD56++ NK細胞、ヘルパーT細胞及びNKT細胞、ならびに血液以外の器官に由来する他の細胞型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。
- 同定される前記細胞を、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、あるいは、
同定される前記細胞を、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PD1+ 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。
- 哺乳類においてPD1+ 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1項に記載の方法を行うことと、さらに、同定された細胞の相対量を、以前に、又は並行して同じ哺乳類から採取されたサンプル、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PD1+ 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PD1+ 細胞を、PDCD1の遺伝子領域のCpG位置のバイサルファイト接近性(到達性)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又は配列番号6〜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6〜配列番号11のいずれかによるオリゴマー、又は配列番号2、配列番号3、配列番号4又は配列番号5による単位複製配列。
- 哺乳動物におけるPD1+ 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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PCT/EP2018/079184 WO2019081590A1 (en) | 2017-10-25 | 2018-10-24 | USE OF MVD AS AN EPIGENETIC MARKER FOR THE IDENTIFICATION OF IMMUNE CELLS, PARTICULARLY NK CD56 + CELLS |
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