JP6668459B2 - 硫酸化多糖類を用いた免疫学的測定法 - Google Patents
硫酸化多糖類を用いた免疫学的測定法 Download PDFInfo
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Description
しかし、安定して臨床検体を測定するために、未だ十分なものでは無かった。
本発明は、生体試料中の測定対象物質(例えば、sIL−2R)を検出する場合に、一般的に多用される、異なる血液凝固阻害剤の使用による血清、ヘパリン加血漿といった被検試料の種類に関わらず、被検試料中の干渉物質の影響を受けることなく安定的で高精度な測定値を得ることができる測定方法及びキットを提供することを目的とする。
[1]生体試料中の測定対象物質を免疫学的に測定する方法において、測定対象物質と該測定対象物質に特異的に結合する抗体との免疫複合体の形成を硫酸化多糖類の存在下で行うことを特徴とする、該測定対象物質を測定する方法、
[2]生体試料中の測定対象物質の免疫学的測定において、抗凝固剤としてヘパリンを添加した血液試料を用いた場合の測定値と、血清を用いた場合の測定値との間の乖離を減少させる方法であって、測定対象物質と該測定対象物質に特異的に結合する抗体との免疫複合体の形成を硫酸化多糖類の存在下で行うことを特徴とする、前記方法、
[3]前記硫酸化多糖類が、デキストラン硫酸、βシクロデキストリン硫酸である、[1]又は[2]の方法、
[4]前記硫酸化多糖類を検体希釈液及び/又は抗体溶液に含有する、[1]〜[3]のいずれかの方法、
[5]前記形成された免疫複合体をB/F分離する工程を含む、[1]〜[4]のいずれかの方法、
[6]測定対象物質に特異的に結合する第1抗体と第2抗体を接触させ、抗原抗体反応により形成された免疫複合体を測定する、[1]〜[5]のいずれかの方法、
[7]測定対象物質が、可溶性インターロイキン2受容体、前立腺特異抗原である、[1]〜[6]のいずれかの方法、
[8][1]〜[7]のいずれかの方法のための、測定対象物質に特異的に結合する抗体と、硫酸化多糖類を含有する緩衝液を含む、該測定対象物質測定キット、
[9]前記抗体として、磁性粒子に担持された前記測定対象物質に特異的に結合する抗体を含む、[8]のキット、
[10]測定対象物質が、可溶性インターロイキン2受容体、前立腺特異抗原である、[8]又は[9]のキット。
例えば、デキストラン硫酸(分子量20,000)は0.000004%以上0.04%以下、デキストラン硫酸(分子量4,000)は0.0004%以上0.04%以下、βシクロデキストリン硫酸塩は0.02%以上0.4%以下等が挙げられる。
参考例1−1:可溶性インターロイキン2受容体測定用試薬の作製と被検試料の調製
可溶性インターロイキン2受容体(sIL−2R)の測定用の試薬を作製した。
全自動臨床検査システム(STACIA:LSIメディエンス社製)による測定
STACIA専用ボトルに、調製した検体希釈液、第1抗体溶液(磁性ラテックス試薬)、第2抗体溶液(酵素標識抗体試薬)をそれぞれ充填し、装置にセットした。以下、前記装置の運転方法に従い、測定した。
具体的には、検体 5μLに検体希釈液50μLを加え、37℃で3.5分間加温した後、第1抗体溶液(磁性ラテックス試薬)25μLを加え、37℃で4.2分間加温した。検体中のsIL−2Rは第1抗体(磁性ラテックス)と反応し、磁性ラテックス−sIL−2R複合体を形成した。次いで、第2抗体溶液(酵素標識抗体試薬)50μLを加え、37℃で4.4分間加温した。第2抗体溶液(ALP標識抗体)を加えると、ALP標識抗体は磁性ラテックス−sIL−2R複合体と反応し、磁性ラテックス−sIL−2R−ALP標識抗体複合体を形成した。洗浄によって未反応の抗体およびsIL−2Rを除去(B/F分離)した後、発光基質液100μLを加え、37℃で 2.7分間反応後に発光量を測定した。CDP−Starを加えると、CDP−Starは複合体中のALPにより加水分解され発光する。検出は、光電子増倍管(PMT)により検出される化学発光基質の発光カウントを測定結果とした。
硫酸化多糖類又は硫酸基を持たない多糖類又は多糖類を持たず硫酸基を含む化合物を、反応液中に下記の濃度になるように検体希釈液に添加したこと以外は、参考例1に従って行った。
・硫酸化多糖類:デキストラン硫酸塩(分子量4000)を、0.04%になるように検体希釈液に添加した。βシクロデキストリン硫酸塩を、0.04%になるように検体希釈液に添加した。
・硫酸基を持たない多糖類:デキストランを、0.04%になるように検体希釈液に添加した。シクロデキストリンを、0.04%になるように検体希釈液に添加した。
・多糖類を持たず硫酸基を含む化合物:CHAPSOを、0.04%になるように検体希釈液に添加した。オクタン酸ナトリウムを、0.04%になるように検体希釈液に添加した。それ以外は、参考例1に従って行った。
以下に記載すること以外は、参考例1の手法に従って行った。
・検体希釈液:0.1mol/L HEPES(8.0)、0.15mol/L NaCl、0.05% Tween20、0.4mmol/L エチレンジアミン四酢酸を含む緩衝液を使用した。
・デキストラン硫酸(分子量20,000)を、反応液中に各濃度(0.0000004、0.000004、0.00004、0.0004、0.004、0.04%)になるように検体希釈液に添加した。
・デキストラン硫酸(分子量4,000)を、反応液中に各濃度(0.000004、0.00004、0.0004、0.004、0.04%)になるように検体希釈液に添加した。
・βシクロデキストリン硫酸塩を、反応液中に各濃度(0.004、0.01、0.02、0.04、0.08、0.2、0.4%)になるように検体希釈液に添加した。
・標準品:組み換えsIL−2Rを100000、40000、2500、500、0U/mLになるように希釈したものを用いた。希釈には0.05mol/L PBS(7.4)、0.05% Tween20、0.1% BSA、0.05% アジ化ナトリウムを含む緩衝液を使用した。該標準品を使用し、公知の方法に従って、発光カウントから各濃度(U/mL)を算出した。
その結果、一致とみなす範囲をマイナス10%〜プラス10%とすると、デキストラン硫酸塩(分子量20,000)は0.000004%以上、デキストラン硫酸(分子量4,000)は0.0004%以上、βシクロデキストリン硫酸塩は0.004%以上添加されることにより、血清およびヘパリン加血漿の可溶性インターロイキン2受容体の反応性が一致することが確認された。
硫酸化多糖類と同様な反応性となるか、硫酸基を持たない多糖類及び多糖類を持たず硫酸基を含む化合物を、同時に反応液中添加して検討した。硫酸基を持たない多糖類及び多糖類を持たず硫酸基を含む化合物を、下記の濃度になるように検体希釈液に添加したこと以外は、参考例1に従って行った。
・多糖類を持たず硫酸基を含む化合物:NDSB−195、NDSB−201、NDSB−256を、それぞれ0.385mmol/L、3.85mmol/Lになるように検体希釈液に添加した。
・多糖類を持たず硫酸基を含む化合物及び硫酸基を持たない多糖類の混合:NDSB−195を3.85mmol/L、及び、デキストラン(分子量2000)を0.19%になるように検体希釈液に添加した。
硫酸基を持たない多糖類及び多糖類を持たず硫酸基を含む化合物を共存させた場合では、実施例1、2の硫酸基を持つ多糖類のような効果は得られず、硫酸基を持つ多糖類を共存させた場合でないとこの高い効果が得られないことは、硫酸基と多糖類の存在によるものではないことから、意外な結果であった。
実施例3−1:total PSA測定用試薬の作製と被検試料の調製
total PSAの測定用の試薬を作製した。
測定対象をtotal PSAとしたこと以外は、参考例1−2と同様に実施した。
その結果を表4に示す。ヘパリン加血漿の濃度を血清の濃度で割った後100を掛けたものを、ヘパリン加血漿/血清として示した。添加無しの例だと、血清およびヘパリン加血漿とでは、total PSAの反応性が異なることがわかった。さらに、一致とみなす範囲をマイナス10%〜プラス10%とすると、βシクロデキストリン硫酸塩は0.002%以上添加されることにより、血清およびヘパリン加血漿のtotal PSAの反応性が一致することが確認された。
以上、本発明を特定の態様に沿って説明したが、当業者に自明の変法や改良は本発明の範囲に含まれる。
Claims (9)
- 生体試料中の測定対象物質の免疫学的測定において、抗凝固剤としてヘパリンを添加した血液試料を用いた場合の測定値と、血清を用いた場合の測定値との間の乖離を減少させる方法であって、測定対象物質と該測定対象物質に特異的に結合する抗体との免疫複合体の形成を硫酸化多糖類の存在下で行うことを特徴とする、前記方法。
- 前記硫酸化多糖類が、デキストラン硫酸、βシクロデキストリン硫酸である、請求項2に記載の方法。
- 前記硫酸化多糖類を検体希釈液及び/又は抗体溶液に含有する、請求項2又は3に記載の方法。
- 前記形成された免疫複合体をB/F分離する工程を含む、請求項2〜4のいずれか一項に記載の方法。
- 測定対象物質に特異的に結合する第1抗体と第2抗体を接触させ、抗原抗体反応により形成された免疫複合体を測定する、請求項2〜5のいずれか一項に記載の方法。
- 測定対象物質が、可溶性インターロイキン2受容体、前立腺特異抗原である、請求項2〜6のいずれか一項に記載の方法。
- 請求項2〜7のいずれか一項に記載の方法のための、測定対象物質に特異的に結合する抗体と、硫酸化多糖類を含有する緩衝液を含む、該測定対象物質測定キット。
- 前記抗体として、磁性粒子に担持された前記測定対象物質に特異的に結合する抗体を含む、請求項8に記載のキット。
- 測定対象物質が、可溶性インターロイキン2受容体、前立腺特異抗原である、請求項8又は9に記載のキット。
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Family Cites Families (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS57182169A (en) | 1981-05-02 | 1982-11-09 | Mitsubishi Chem Ind Ltd | Measuring method for antigen-antibody reaction |
US4707443A (en) | 1985-04-19 | 1987-11-17 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Soluble interleukin-2 receptor as a disease indicator and a method of assaying the same |
US4829009A (en) * | 1986-02-21 | 1989-05-09 | The Regents Of The University Of California | Noise controlled immunoassays |
US5189067A (en) | 1991-04-11 | 1993-02-23 | Dow Corning Corporation | Skin treatment with siliconates |
WO1992021769A1 (en) * | 1991-05-30 | 1992-12-10 | Abbott Laboratories | Reagents containing a nonspecific binding blocker in ion-capture binding assays |
JPH05189067A (ja) | 1992-01-09 | 1993-07-30 | Nissin Electric Co Ltd | 電圧変動抑制装置の制御方式 |
US5466580A (en) * | 1993-09-22 | 1995-11-14 | Xoma Corporation | Method for quantifying BPI in body fluids |
JPH08226920A (ja) | 1995-02-20 | 1996-09-03 | Masashi Funayama | グリコヘモグロビンおよびフルクトサミンの定量方法 |
US6656508B2 (en) | 1997-04-17 | 2003-12-02 | Amgen Inc. | Sustained-release alginate gels |
FR2774473B1 (fr) | 1998-02-05 | 2000-05-12 | Pasteur Sanofi Diagnostics | Procede de dosage des troponines dans des milieux biologiques permettant d'eviter les interferences dues a l'heparine |
WO2002027316A2 (en) * | 2000-09-25 | 2002-04-04 | Abbott Laboratories | Methods and kits for decreasing interferences of assays samples containing plasma or serum in specific binding assays by using a large polycation |
WO2002063302A1 (en) | 2001-02-07 | 2002-08-15 | Immunomatrix Inc. | A method for reducing heparin interference in diagnostic tests for cardiac troponin |
BRPI0307976B8 (pt) | 2002-02-28 | 2021-07-27 | Microsens Biophage Ltd | processo para a ligação seletiva de uma forma anormal agregativa de uma proteína, e, processo ou ensaio quanto à presença de uma forma agregativa anormal de uma proteína de uma amostra |
CA2515850A1 (en) | 2003-04-14 | 2004-10-28 | Caliper Life Sciences, Inc. | Reduction of migration shift assay interference |
TW200604527A (en) | 2004-06-14 | 2006-02-01 | Kyowa Medex Co Ltd | An immunological method and reagent for determing the inhibited nonspecific reaction |
JP2007170992A (ja) | 2005-12-22 | 2007-07-05 | Abbott Japan Co Ltd | ホモシステインの免疫学的測定方法 |
US8617820B2 (en) * | 2007-08-28 | 2013-12-31 | Ortho-Clinical Diagnostics, Inc. | Use of glycosaminoglycans to reduce non-specific binding in immunoassays |
WO2010001619A1 (ja) * | 2008-07-04 | 2010-01-07 | 積水メディカル株式会社 | 免疫学的測定における感度増強方法又はヘモグロビンの影響回避方法 |
EP2312308B1 (en) | 2008-07-22 | 2016-08-31 | ARKRAY, Inc. | Apparatus and method for analysis by capillary electrophoretic method |
JP2010107363A (ja) | 2008-10-30 | 2010-05-13 | Sysmex Corp | トロポニンiの測定方法及び測定用試薬キット |
JP2010127827A (ja) * | 2008-11-28 | 2010-06-10 | Abbott Japan Co Ltd | 非特異的相互作用抑制剤及びその診断測定系への応用 |
JP5674339B2 (ja) | 2009-05-22 | 2015-02-25 | 協和メデックス株式会社 | 可溶性インターロイキン−2受容体の測定方法及び測定用試薬 |
US10088490B2 (en) | 2010-08-20 | 2018-10-02 | Siemens Healthcare Diagnostics Inc. | Assay for analytes using multiple receptors |
WO2012115221A1 (ja) * | 2011-02-25 | 2012-08-30 | 三菱化学メディエンス株式会社 | 心筋トロポニンの測定法 |
WO2013012954A2 (en) | 2011-07-19 | 2013-01-24 | Baxter International Inc. | Resorption enhancers as additives to improve the oral formulation of non-anticoagulant sulfated polysaccharides |
JP6116268B2 (ja) * | 2013-01-31 | 2017-04-19 | デンカ生研株式会社 | 生体粘膜由来検体測定イムノアッセイにおいて偽陰性を抑制する方法 |
US20140273021A1 (en) * | 2013-03-14 | 2014-09-18 | Enzo Biochem, Inc. | Vitamin d assays |
JP2013152247A (ja) | 2013-04-12 | 2013-08-08 | Abbott Japan Co Ltd | 非特異的相互作用抑制剤及びその診断測定系への応用 |
JP6651794B2 (ja) * | 2015-11-05 | 2020-02-19 | 富士レビオ株式会社 | 心筋トロポニンi測定試薬及び方法 |
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