JP5015318B2 - Gdf−15及びナトリウム利尿ペプチドを用いた、心房細動を有する患者の心不全を評価するための手段及び方法 - Google Patents
Gdf−15及びナトリウム利尿ペプチドを用いた、心房細動を有する患者の心不全を評価するための手段及び方法 Download PDFInfo
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/475—Assays involving growth factors
- G01N2333/495—Transforming growth factor [TGF]
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/575—Hormones
- G01N2333/58—Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Brain natriuretic peptide [BNP, proBNP]; Cardionatrin; Cardiodilatin
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/32—Cardiovascular disorders
- G01N2800/324—Coronary artery diseases, e.g. angina pectoris, myocardial infarction
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/32—Cardiovascular disorders
- G01N2800/325—Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
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- Peptides Or Proteins (AREA)
Description
(a)該被験体のサンプル中のGDF-15の量を測定するステップ、及び
(b)ステップ(a)で測定したGDF-15の量を適切な参照量と比較し、それによって心不全を診断するステップ
を含む方法に関する。
(a)心房細動を示す被験体のサンプル中のGDF-15の量を測定するための手段;及び
(b)(a)の手段によって測定された量を適切な参照量と比較して、心不全の診断が可能となる手段
を含むデバイスに関する。
(a)心房細動を示す被験体のサンプル中のGDF-15の量を測定するための手段;及び
(b)(a)の手段によって測定された量を適切な参照量と比較して、心不全の診断が可能となる手段
とを含むキットに関する。
血清サンプル及び血漿サンプル中のGDF-15及びNT-proBNPの測定
血清サンプル及び血漿サンプル中のGDF-15の濃度を測定するために、GDF-15アフィニティークロマトグラフィーで精製したポリクローナルヤギ抗ヒトGDF-15 IgG抗体(R&D Systems;AF957)を用いて免疫放射定量分析アッセイ(IRMA)を開発した。Maxisorp Startubes (Nunc)を、0.1 Mの炭酸ナトリウムバッファー(pH 9.0)中の0.5μgの抗GDF-15 IgGにより4℃で一晩かけてコーティングした後、0.1%Tween 20を添加したリン酸緩衝生理食塩水で2回洗った。血清サンプル又は血漿サンプル(100 μL)をアッセイバッファー(30 g/L BSA、10 g/LウシIgG、1%ヤギ血清、0.1%アジ化ナトリウム、1 M NaCl、40 mM リン酸ナトリウムバッファー, pH 7.4)で1:1に希釈し、試験管に入れ、4℃で16時間インキュベートした。2回の洗浄ステップの後、10 ngの[125I]ヨウ素化抗GDF-15 IgG(比活性 0.74 MBq/μg)を200μLのアッセイバッファーで希釈し、これを各試験管に添加して、室温で4時間インキュベートした。3回の最終洗浄ステップ後、結合している放射活性をガンマカウンター(LKB Wallac 1261)で定量した。各実験において、R&D Systemsの組換えヒトGDF-15(957-GD/CF)を用いて標準曲線を作成した。組換えGDF-15タンパク質の新しいバッチでの結果は標準血漿サンプルで試験し、10%を超える偏差は、このアッセイのために調整係数を導入して補正した。同一の患者から得た血清サンプル及び血漿サンプル中のGDF-15の測定は、最終的な希釈係数について補正した後には実質的に同一の結果を生じた。このアッセイの検出限界は20 pg/mLであった。アッセイ内変動係数は、744、1518、及び8618 pg/mLの平均GDF-15レベルについてそれぞれ5.6、5.9、及び6.5%であった。アッセイ間変動係数は、832、4739、及び9230 pg/mLの平均GDF-15レベルについてそれぞれ8.6、5.7、及び4.4%であった。
心房細動によりNT-proBNPレベルは影響を受けるが、GDF-15レベルは影響を受けない
心電図記録法によって調べた際に洞調律を有する合計273人の患者について、GDF-15レベル及びNTproBNPレベルの変化を分析した。心房細動を示す合計17人の患者についても同じ分析を行った。さらに、左心室駆出分画率を測定した。
Claims (6)
- 心房細動を示す被験体において心不全を検出する方法であって、
(a)該被験体のサンプル中のGDF-15の量を測定するステップ、及び
(b)心不全を検出するために、ステップ(a)で測定したGDF-15の量をGDF-15の参照量と比較するステップ
を含み、該参照量が、心不全に罹患していない、心房細動を示す被験体のサンプル中で測定されたGDF-15の量である、上記方法。 - 心不全が60%未満の左心室駆出分画率(LVEF)を伴う、請求項1に記載の方法。
- ステップ(a)で測定したGDF-15の量が参照量より多いことは、心不全を示す、請求項1または2に記載の方法。
- 被験体がヒトである、請求項1〜3のいずれか1項に記載の方法。
- 心房細動を示す被験体において心不全を検出するためのデバイスであって、
(a)心房細動を示す被験体のサンプル中のGDF-15の量を測定するための手段;及び
(b)(a)の手段によって測定された量をGDF-15の参照量と比較して、心不全の検出が可能となる手段
を含み、該参照量が、心不全に罹患していない、心房細動を示す被験体のサンプル中で測定されたGDF-15の量である、上記デバイス。 - 請求項1〜4のいずれか1項に記載の方法を実施するために採用されるキットであって、該方法を行うための取扱説明書と、
(a)心房細動を示す被験体のサンプル中のGDF-15の量を測定するための手段;及び
(b)(a)の手段によって測定された量をGDF-15の参照量と比較して、心不全の検出が可能となる手段
とを含むキット。
Applications Claiming Priority (3)
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EP07108852.0 | 2007-05-24 | ||
EP07108852A EP1995596B1 (en) | 2007-05-24 | 2007-05-24 | Methods for assessing heart failure in patients with atrial fibrillation using GDF-15 |
PCT/EP2008/056261 WO2008142110A1 (en) | 2007-05-24 | 2008-05-21 | Means and methods for assessing heart failure in patients with atrial fibrillation using gdf-15 and natriuretic peptides |
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EP (1) | EP1995596B1 (ja) |
JP (1) | JP5015318B2 (ja) |
AT (1) | ATE537454T1 (ja) |
ES (1) | ES2379104T3 (ja) |
WO (1) | WO2008142110A1 (ja) |
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EP2195660A1 (en) * | 2007-08-30 | 2010-06-16 | Roche Diagnostics GmbH | Means and methods for the discrimination of gdf-15 elevation related or unrelated to cardiac disorders |
EP2227696A1 (en) * | 2008-01-08 | 2010-09-15 | Roche Diagnostics GmbH | Means and methods for assessing the risk of patients presenting to emergency units based on gdf-15 |
CN102549436A (zh) | 2009-07-27 | 2012-07-04 | 霍夫曼-拉罗奇有限公司 | mimecan在评价心力衰竭中的用途 |
EP2491401B1 (en) * | 2009-10-21 | 2018-06-06 | Mycartis N.V. | Mcam as a biomarker for fluid homeostasis |
EP2439535A1 (en) * | 2010-10-07 | 2012-04-11 | F. Hoffmann-La Roche AG | Diagnosis of diabetes related heart disease and GDF-15 and Troponin as predictors for the development of type 2 diabetes mellitus |
KR101230088B1 (ko) | 2010-11-24 | 2013-02-05 | 연세대학교 산학협력단 | 심방세동의 예후 예측 방법 |
AU2015273097A1 (en) * | 2014-06-13 | 2016-11-17 | Novartis Ag | Use of serelaxin to reduce GDF-15 |
EP3425392A4 (en) | 2016-02-29 | 2020-02-05 | Public University Corporation Yokohama City University | METHOD FOR DETECTING CASTRATION-RESISTANT PROSTATE CANCER AND REAGENT REAGENT |
EP3472622B1 (en) * | 2016-06-17 | 2020-08-05 | Roche Diagnostics GmbH | Circulating angiopoietin-2 (ang-2) for the prediction of recurrence of atrial fibrillation |
WO2018167447A1 (en) | 2017-03-14 | 2018-09-20 | University Of Sheffield | Low dose aspirin (1-50 mg) together with antiplatelets such as ticagrelor of anticoagulants |
JP7127422B2 (ja) | 2017-08-30 | 2022-08-30 | 東ソー株式会社 | 癌を検出する方法及び検出試薬 |
JP7419341B2 (ja) * | 2018-07-31 | 2024-01-22 | エフ. ホフマン-ラ ロシュ アーゲー | 心房細動の評価における循環DKK3(Dickkopf関連タンパク質3) |
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CA2598582A1 (en) * | 2005-02-17 | 2006-08-24 | Georg Hess | Use of nt-proanp/nt-probnp ratio for diagnosing cardiac dysfunctions |
WO2008015254A2 (en) * | 2006-08-04 | 2008-02-07 | Medizinische Hochschule Hannover | Means and methods for assessing the risk of cardiac interventions based on gdf-15 |
EP2195660A1 (en) * | 2007-08-30 | 2010-06-16 | Roche Diagnostics GmbH | Means and methods for the discrimination of gdf-15 elevation related or unrelated to cardiac disorders |
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US7955854B2 (en) | 2011-06-07 |
WO2008142110A1 (en) | 2008-11-27 |
US20100159608A1 (en) | 2010-06-24 |
ES2379104T3 (es) | 2012-04-20 |
ATE537454T1 (de) | 2011-12-15 |
EP1995596A1 (en) | 2008-11-26 |
JP2010528275A (ja) | 2010-08-19 |
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