JP4495168B2 - 抗ccpおよびインターロイキン6の測定による慢性関節リウマチの評価方法 - Google Patents
抗ccpおよびインターロイキン6の測定による慢性関節リウマチの評価方法 Download PDFInfo
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- JP4495168B2 JP4495168B2 JP2006546031A JP2006546031A JP4495168B2 JP 4495168 B2 JP4495168 B2 JP 4495168B2 JP 2006546031 A JP2006546031 A JP 2006546031A JP 2006546031 A JP2006546031 A JP 2006546031A JP 4495168 B2 JP4495168 B2 JP 4495168B2
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- Prior art keywords
- ccp
- marker
- rheumatoid arthritis
- markers
- interleukin
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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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- 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
- G01N33/6869—Interleukin
Description
試験母集団
389例の高度にRAの特徴を示す患者(最長疾患持続期間15年)由来の試料を欧州の5つのセンターにおいて収集し、2年の追跡調査を行なった。すべての個体は、ARA基準に従ってRA患者と診断され、ARA判別基準(Hochberg, M.C.ら, Arthritis Rheum. 35 (1992) 498-502) により判別すると≦IIIの機能(functional)状態を有した。すべての患者について、徹底(extensive)症例報告書(=CRF)に記録した。CRFは、健康評価アンケート(Health Assessment Questionnaire)、SF36アンケート、腫脹した圧痛のある関節の数、Larsen スコア、実験パラメータ、関連する外科処置の病歴、投薬、共存症および共存症に関する投薬を含んだ。標準的な処置の後、毎年、X線撮影を行なった。この研究に含めた被験体から得たベースライン試料のみを本解析に含めた。
測定したマーカー
表2は、使用したアッセイの選択を示し、研究形式ならびにアッセイの供給業者を示す。アッセイのほとんどは、手動式マイクロタイタープレート形式(=MTP)ELISAであった。RFおよびCRPを、同じような試験形式で自動Hitachiアナライザーにて測定した。血清試料のマーカー濃度を、これらの市販のアッセイにより、患者ならびに対照について測定した。
統計学的評価
患者コホートを、訓練集合(training set)(約67%)と試験集合(約33%)に無作為に分けた。訓練集合に関して判別アルゴリズムを開発し、独立した試験集合に関して、このアルゴリズムを検証した。表3からわかるように、それぞれの集合は、規模および年齢をかなり適合させた。
RAの診断のためのマーカーパネルの同定
表4は、訓練集団に関する対照(OAを含む)に対するRAと診断された患者の判別結果を表す。アルゴリズムを中止したとき、選択された第1のマーカーは抗CCP、第2のものはIL-6、および第3の最後のものはヒアルロン酸であった。
また、抗CCP、IL-6およびSAAのマーカーの組合せは、抗CCP、IL-6およびヒアルロン酸の組合せによる狭いマージン(narrow margin)よってのみ予想(bet)されたため、この判別結果も報告する。参照として、全RF(これは、前述のように、現在、ARA基準の一部を構成する唯一の生化学的マーカーである)の判別結果を示す。
Al-Dehaimi, A.W.ら, Clin. Chem. 45 (1999) 676-681
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WO 01/46222
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WO 98/08946
WO 98/22503
WO 99/28344
WO 99/35167
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Claims (7)
- a)試料中の、少なくとも抗CCPおよびインターロイキン6の濃度値を測定すること、b)工程a)で測定した濃度値を、判別分析(Discriminant analysis)、カーネル法(Kernel Methods)、ノンパラメトリック法(Nonparametric Methods)、PLS(Partial Least Squares)、ツリーベースの方法(Tree-Based Methods)、または一般線型モデル(Generalized Linear Models)を使用して、数学的に組み合わせること、ならびに
c) 工程b)の組み合わせた値を慢性関節リウマチの有無と相関させること、ここで、組み合わせた値の上昇は、慢性関節リウマチの存在を示す
を含む、生化学的マーカーによる慢性関節リウマチの有無のインビトロ評価方法。 - CRP、SAA、S100、オステオポンチン、RF、MMP-1、MMP-3、ヒアルロン酸、sCD14、脈管形成マーカー、および骨、軟骨または滑膜代謝の産物からなる群より選択される少なくとも1種のさらなるマーカーの測定をさらに含む、請求項1記載の方法。
- 前記さらなるマーカーがマーカーSAAである、請求項2記載の方法。
- 少なくとも抗CCPおよびインターロイキン6を含むマーカーパネルの、請求項1記載の方法による慢性関節リウマチの検出における使用。
- 該マーカーパネルが、抗CCP、インターロイキン6、ならびにCRP、SAA、S100、オステオポンチン、RF、MMP-1、MMP-3、ヒアルロン酸、sCD14、脈管形成マーカー、および骨、軟骨または滑膜代謝の産物からなる群より選択される少なくとも1種のさらなるマーカーを含む、請求項4記載の使用。
- 少なくとも抗CCP、インターロイキン6およびマーカーSAAを含むマーカーパネルの、請求項3記載の方法による慢性関節リウマチの検出における使用。
- 抗CCPおよびインターロイキン6をそれぞれ特異的に測定するのに必要な試薬ならびに、任意に、測定を行なうための補助試薬とを含む、請求項1記載の方法を行なうためのキット。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03029658 | 2003-12-23 | ||
PCT/EP2004/014527 WO2005064307A2 (en) | 2003-12-23 | 2004-12-21 | Method of assessing rheumatoid arthritis by measuring anti-ccp and interleukin 6 |
Publications (2)
Publication Number | Publication Date |
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JP2007515647A JP2007515647A (ja) | 2007-06-14 |
JP4495168B2 true JP4495168B2 (ja) | 2010-06-30 |
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Application Number | Title | Priority Date | Filing Date |
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JP2006546031A Expired - Fee Related JP4495168B2 (ja) | 2003-12-23 | 2004-12-21 | 抗ccpおよびインターロイキン6の測定による慢性関節リウマチの評価方法 |
Country Status (13)
Country | Link |
---|---|
US (1) | US7846674B2 (ja) |
EP (2) | EP1700129B1 (ja) |
JP (1) | JP4495168B2 (ja) |
AT (1) | ATE458201T1 (ja) |
CA (1) | CA2546312C (ja) |
CY (1) | CY1111229T1 (ja) |
DE (2) | DE602004010432T2 (ja) |
DK (1) | DK1882946T3 (ja) |
ES (2) | ES2297521T3 (ja) |
PL (1) | PL1882946T3 (ja) |
PT (1) | PT1882946E (ja) |
SI (1) | SI1882946T1 (ja) |
WO (1) | WO2005064307A2 (ja) |
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JP2008538007A (ja) | 2005-04-15 | 2008-10-02 | ベクトン,ディッキンソン アンド カンパニー | 敗血症の診断 |
US7901896B2 (en) * | 2005-07-21 | 2011-03-08 | Wayne State University | Asbestos exposure, pleural mesothelioma, and osteopontin levels |
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US20090142792A1 (en) * | 2007-06-21 | 2009-06-04 | Robinson William H | Biomarkers for the diagnosis of autoimmune disease |
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ES2584438T3 (es) | 2008-03-21 | 2016-09-27 | Universiteit Hasselt | Biomarcadores para artritis reumatoide |
WO2009123737A2 (en) | 2008-04-03 | 2009-10-08 | Becton, Dickinson And Company | Advanced detection of sepsis |
WO2010075249A2 (en) | 2008-12-22 | 2010-07-01 | Genentech, Inc. | A method for treating rheumatoid arthritis with b-cell antagonists |
EP2204655A1 (en) | 2008-12-23 | 2010-07-07 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Diagnostic prediction of rheumatoid arthritis and systemic lupus erythematosus |
CN101988924B (zh) * | 2009-07-31 | 2014-06-11 | 上海科新生物技术股份有限公司 | 检测血液抗环瓜氨酸多肽抗体的试纸条及制备方法 |
CN102507918B (zh) * | 2011-11-09 | 2014-10-29 | 四川新健康成生物股份有限公司 | 抗环瓜氨酸肽抗体测定试剂盒 |
WO2015009754A2 (en) | 2013-07-15 | 2015-01-22 | Svoboda Steven J | Methods and apparatus for assessment of risk for joint injury |
JP6220222B2 (ja) | 2013-10-28 | 2017-10-25 | シスメックス株式会社 | 関節リウマチの診断を補助するための方法、システム及びコンピュータプログラム製品 |
WO2016128348A1 (en) | 2015-02-13 | 2016-08-18 | F. Hoffmann-La Roche Ag | Method of assessing rheumatoid arthritis by measuring anti-ccp and anti-pik3cd |
CA2985637A1 (en) | 2015-05-12 | 2016-11-17 | The General Hospital Corporation | Autoantigens for diagnosis of rheumatoid arthritis |
US10908159B2 (en) | 2016-06-07 | 2021-02-02 | The General Hospital Corporation | Identification of a T cell epitope of Prevotella copri that induces T cell responses in patients with Rheumatoid arthritis |
CN109929009B (zh) * | 2019-03-20 | 2021-06-04 | 深圳市新产业生物医学工程股份有限公司 | Ccp肽段、包含其的抗原、试剂、试剂盒及应用 |
US11367521B1 (en) | 2020-12-29 | 2022-06-21 | Kpn Innovations, Llc. | System and method for generating a mesodermal outline nourishment program |
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2004
- 2004-12-21 ES ES04804125T patent/ES2297521T3/es active Active
- 2004-12-21 EP EP04804125A patent/EP1700129B1/en not_active Not-in-force
- 2004-12-21 SI SI200431398T patent/SI1882946T1/sl unknown
- 2004-12-21 ES ES07019998T patent/ES2340328T3/es active Active
- 2004-12-21 CA CA2546312A patent/CA2546312C/en active Active
- 2004-12-21 DK DK07019998.9T patent/DK1882946T3/da active
- 2004-12-21 WO PCT/EP2004/014527 patent/WO2005064307A2/en active IP Right Grant
- 2004-12-21 AT AT07019998T patent/ATE458201T1/de active
- 2004-12-21 EP EP07019998A patent/EP1882946B1/en not_active Not-in-force
- 2004-12-21 PL PL07019998T patent/PL1882946T3/pl unknown
- 2004-12-21 JP JP2006546031A patent/JP4495168B2/ja not_active Expired - Fee Related
- 2004-12-21 DE DE602004010432T patent/DE602004010432T2/de active Active
- 2004-12-21 DE DE602004025636T patent/DE602004025636D1/de active Active
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Also Published As
Publication number | Publication date |
---|---|
ES2297521T3 (es) | 2008-05-01 |
EP1700129A2 (en) | 2006-09-13 |
CA2546312C (en) | 2010-11-09 |
WO2005064307A2 (en) | 2005-07-14 |
SI1882946T1 (sl) | 2010-06-30 |
ES2340328T3 (es) | 2010-06-01 |
JP2007515647A (ja) | 2007-06-14 |
WO2005064307A3 (en) | 2005-09-01 |
DE602004025636D1 (de) | 2010-04-01 |
ATE458201T1 (de) | 2010-03-15 |
EP1882946A2 (en) | 2008-01-30 |
US20070264673A1 (en) | 2007-11-15 |
CY1111229T1 (el) | 2015-06-11 |
EP1882946A3 (en) | 2008-02-13 |
EP1700129B1 (en) | 2007-11-28 |
CA2546312A1 (en) | 2005-07-14 |
DE602004010432T2 (de) | 2008-12-04 |
EP1882946B1 (en) | 2010-02-17 |
DK1882946T3 (da) | 2010-05-31 |
PL1882946T3 (pl) | 2010-07-30 |
US7846674B2 (en) | 2010-12-07 |
DE602004010432D1 (de) | 2008-01-10 |
PT1882946E (pt) | 2010-04-21 |
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