DK2391654T3 - Urin- og serumbiomarkører associeret med diabetisk nefropati - Google Patents
Urin- og serumbiomarkører associeret med diabetisk nefropati Download PDFInfo
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- DK2391654T3 DK2391654T3 DK10735454.0T DK10735454T DK2391654T3 DK 2391654 T3 DK2391654 T3 DK 2391654T3 DK 10735454 T DK10735454 T DK 10735454T DK 2391654 T3 DK2391654 T3 DK 2391654T3
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Claims (32)
1. Fremgangsmåde til at diagnosticere diabetisk nefropati hos et individ, omfattende: at bestemme et niveau afen biomarkør i en urinprøve fra et individ mistænkt for at have diabetisk nefropati, hvor biomarkøren er et fragment af alpha-2-HS-glycoprotein valgt fra gruppen bestående af WSLGSPSGEVSHPRKT (SEQ ID NO:l) og MGWSLGSPSGEVSHPRKT (SEQ ID NO:2), og at vurdere hvorvidt individet har diabetisk nefropati baseret på niveauet af biomarkøren; hvor en stigning i niveauet af biomarkøren, sammenlignet med det hos et individ uden diabetisk nefropati, indikererat individet har diabetisk nefropati.
2. Fremgangsmåden ifølge krav 1, endvidere omfattende at bestemme et niveau af en anden biomarkør i urinprøven fra individet, hvor den anden biomarkør er et fragment af alpha-1 antitrypsin valgt fra gruppen bestående af KGKWERPFEVKDTEEEDF (SEQ ID NO:3), MIEQNTKSPLFMGKWNPTQK (SEQ ID NO:4), EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAE (SEQ ID NO:5), og EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFA (SEQ ID NO:6).
3. Fremgangsmåden ifølge kravene 1 eller 2, endvidere omfattende at bestemme et niveau af en biomarkør i urinprøven fra individet, hvor biomarkøren er GQEHFAHLLILRDTKTYMLAFDVNDEKNWGLS (SEQ ID NO:7).
4. Fremgangsmåden ifølge kravene 1 til 3, endvidere omfattende at bestemme et niveau af et fragment af osteopontin i en serumprøve fra individet, hvor fragmentet af osteopontin er valgt fra gruppen bestående af YPDAVATWLNPDPSQKQNLLAPQNAVSSEETNDFKQETLPSK (SEQ ID NO:8) og KYPDAVATWLNPDPSQKQNLLAPQTLPSK (SEQ ID NO:9).
5. Fremgangsmåden ifølge kravene 1 til 4, endvidere omfattende, efter vurderingstrinnet, at korrelere niveauet af biomarkøren med diabetisk nefropati status, hvor en stigning i biomarkør-niveauet, i forhold til det hos et individ uden diabetisk nefropati, indikerer at individet er i sent stadie diabetisk nefropati.
6. Fremgangsmåde til at vurdere effektiviteten afen diabetisk nefropati-behandling i et individ, omfattende: at bestemme et præbehandlings-niveau afen biomarkør i en urinprøve fra individet, hvor biomarkøren er et fragment af alpha-2-HS-glycoprotein valgt fra gruppen bestående af VVSLGSPSGEVSHPRKT (SEQ ID NO:l) og MGVVSLGSPSGEVSHPRKT (SEQ ID NO:2), at bestemme et postbehandlings-niveau af biomarkøren i en urinprøve fra individet; og at vurdere effektiviteten af behandlingen baseret på en ændring i niveauet af biomarkøren efter behandlingen, hvor i det tilfælde at postbehandlings-niveauet af biomarkøren er det samme eller lavere end præbehandlings-niveauet af biomarkøren, så er det en indikation på at behandlingen er effektiv.
7. Fremgangsmåden ifølge krav 6, endvidere omfattende at bestemme et niveau af en anden biomarkør i urinprøven fra individet, hvor den anden biomarkør er et fragment af alpha-1 antitrypsin valgt fra gruppen bestående af KGKWERPFEVKDTEEEDF (SEQ ID NO:3), MIEQNTKSPLFMGKVVNPTQK (SEQ ID NO:4), EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAE (SEQ ID NO:5), og EDPQGDAAQKTDTSΗHDQDHPTFNKITPNLAEFA (SEQ ID NO:6).
8. Fremgangsmåden ifølge krav 6 eller 7, endvidere omfattende at bestemme et niveau af en tredje biomarkør i urinprøven fra individet, hvor den tredje biomarkør er GQEHFAHLLILRDTKTYMLAFDVNDEKNWGLS (SEQ ID NO:7).
9. Fremgangsmåden ifølge kravene 6 til 8, endvidere omfattende at bestemme et niveau af et fragment af osteopontin i en serumprøve fra individet, hvor fragmentet af osteopontin er valgt fra gruppen bestående af YPDAVATWLNPDPSQKQNLLAPQNAVSSEETNDFKQETLPSK (SEQ ID NO:8) og KYPDAVATWLNPDPSQKQNLLAPQTLPSK (SEQ ID NO:9).
10. Fremgangsmåden ifølge kravene 6 til 9, hvor individet er en human patient.
11. Fremgangsmåden ifølge kravene 6 til 9, hvor individet er et laboratoriedyr.
12. Fremgangsmåde til at bestemme et diabetisk nefropati-stadie i et individ, omfattende: at bestemme et niveau af en biomarkør i en urinprøve fra et individ mistænkt for at have diabetisk nefropati og, eventuelt, en eller flere kliniske faktorer, hvor biomarkøren er et fragment af alpha-2-HS-glycoprotein valgt fra gruppen bestående af WSLGSPSGEVSHPRKT (SEQ ID NO: 1) og MGWSLGSPSGEVSHPRKT (SEQ ID NO:2), og de kliniske faktorer vælges fra gruppen bestående af alder, køn, HbAlc, albumin/kreatinin-forhold, og glomerulær filtrationshastighed; at beregne en sygdomsscore baseret på niveauet af biomarkøren; og at vurdere individets diabetisk nefropati stadie baseret på sygdomsscoren sammenlignet med forudbestemte skærings-værdier, hvor en stigning i sygdomsscoren, sammenlignet med forudbestemte skærings-værdier, indikerer at individet er i et sent stadie af diabetisk nefropati.
13. Fremgangsmåden ifølge krav 12, endvidere omfattende at bestemme et niveau af en anden biomarkør i urinprøven fra individet, hvor den anden biomarkør er et fragment af alpha-1 antitrypsin valgt fra gruppen bestående af KGKWERPFEVKDTEEEDF (SEQ ID NO:3), MIEQNTKSPLFMGKWNPTQK (SEQ ID N0:4), EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAE (SEQ ID N0:5), og EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFA (SEQ ID N0:6).
14. Fremgangsmåden ifølge krav 12 eller 13, endvidere omfattende at bestemme et niveau af en tredje biomarkør i urinprøven fra individet, hvor den tredje biomarkør er GQEHFAHLLILRDTKTYMLAFDVNDEKNWGLS (SEQ ID N0:7).
15. Fremgangsmåden ifølge kravene 12 til 14, endvidere omfattende at bestemme et niveau af et fragment af osteopontin i en serumprøve fra individet, hvor fragmentet af osteopontin er valgt fra gruppen bestående af YPDAVATWLNPDPSQKQNLLAPQNAVSSEETNDFKQETLPSK (SEQ ID NO:8) og KYPDAVATWLNPDPSQKQNLLAPQTLPSK (SEQ ID NO:9).
16. Fremgangsmåden ifølge kravene 12 til 15, hvor sygdomsscoren beregnes ved en analyse valgt fra gruppen bestående af ridge regressionsanalyse, faktoranalyse, diskriminant funktionsanalyse, og logistisk regressionsanalyse.
17. Fremgangsmåde til at overvåge udviklingen af diabetisk nefropati i et individ, omfattende: at opnå en første urinprøve fra et individ mistænkt for at have diabetisk nefropati; at opnå en anden urinprøve fra individet 2 uger til 12 måneder senere; at bestemme i den første og anden prøve et niveau af en biomarkør, hvor biomarkøren er et fragment af alpha-2-HS-glycoprotein valgt fra gruppen bestående af VVSLGSPSGEVSHPRKT (SEQ ID NO:l) og MGVVSLGSPSGEVSHPRKT (SEQ ID NO:2), og de kliniske faktorer vælges fra gruppen bestående af alder, køn, HbAlc, albumin/kreatinin-forhold, og glomerulær filtrationshastighed; at beregne en første sygdomsscore og en anden sygdomsscore baseret på niveauerne af biomarkøren, og eventuelt, en eller flere kliniske faktorer, henholdsvis i den første og anden prøve; og at vurdere sygdomsudvikling i individet, hvor i det tilfælde at den anden sygdomsscore er større end den første sygdomsscore, da er det en indikation på en forværring af diabetisk nefropati.
18. Fremgangsmåden ifølge krav 17, endvidere omfattende at bestemme et niveau af en anden biomarkør i urinprøven fra individet, hvor den anden biomarkør er et fragment af alpha-1 antitrypsin valgt fra gruppen bestående af KGKWERPFEVKDTEEEDF (SEQ ID NO:3), MIEQNTKSPLFMGKVVNPTQK (SEQ ID NO:4), EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAE (SEQ ID NO:5), og EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFA (SEQ ID NO:6).
19. Fremgangsmåden ifølge krav 17 eller 18, endvidere omfattende at bestemme et niveau af en tredje biomarkør i urinprøven fra individet, hvor den tredje biomarkør er GQEHFAHLLILRDTKTYMLAFDVNDEKNWGLS (SEQ ID NO:7).
20. Fremgangsmåden ifølge kravene 17 til 19, endvidere omfattende at bestemme et niveau af et fragment af osteopontin i en serumprøve fra individet, hvor fragmentet af osteopontin er valgt fra gruppen bestående af YPDAVATWLNPDPSQKQNLLAPQNAVSSEETNDFKQETLPSK (SEQ ID NO:8) og KYPDAVATWLNPDPSQKQNLLAPQTLPSK (SEQ ID NO:9).
21. Fremgangsmåden ifølge kravene 17 til 20, hvor sygdomsscoren beregnes ved en analyse valgt fra gruppen bestående af ridge regressionsanalyse, faktoranalyse, diskriminant funktionsanalyse, og logistisk regressionsanalyse.
22. Fremgangsmåde til at vurdere effektiviteten afen diabetisk nefropati-behandling i et individ, omfattende: at opnå en første urinprøve fra individet før behandlingen, at opnå en anden urinprøve fra individet efter behandlingen, at bestemme niveauerne afen biomarkør i prøverne, hvor biomarkøren er et fragment af alpha-2-HS-glycoprotein valgt fra gruppen bestående af VVSLGSPSGEVSHPRKT (SEQ ID NO:l) og MGVVSLGSPSGEVSHPRKT (SEQ ID NO: 2), og de kliniske faktorer vælges fra gruppen bestående af alder, køn, HbAlc, albumin/kreatinin-forhold, og glomerulær filtrationshastighed; at beregne en første sygdomsscore og en anden sygdomsscore baseret på niveauerne af biomarkører og, eventuelt, en eller flere kliniske faktorer, i den første og anden prøve, henholdsvis; og at vurdere effektiviteten af behandlingen i individet, hvor i det tilfælde at den anden sygdomsscore er lig med eller lavere end den første sygdomsscore, da er det en indikation på en effektiv behandling.
23. Fremgangsmåden ifølge krav 22, endvidere omfattende at bestemme et niveau af en anden biomarkør i urinprøven fra individet, hvor den anden biomarkør er et fragment af alpha-1 antitrypsin valgt fra gruppen bestående af KGKWERPFEVKDTEEEDF (SEQ ID NO:3), MIEQNTKSPLFMGKWNPTQK (SEQ ID NO:4), EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAE (SEQ ID NO:5), og EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFA (SEQ ID NO:6).
24. Fremgangsmåden ifølge krav 22 eller 23, endvidere omfattende at bestemme et niveau af en tredje biomarkør i urinprøven fra individet, hvor den tredje biomarkør er GQEHFAHLLILRDTKTYMLAFDVNDEKNWGLS (SEQ ID NO:7).
25. Fremgangsmåden ifølge kravene 22 til 24, endvidere omfattende at bestemme et niveau af et fragment af osteopontin i en serumprøve fra individet, hvor fragmentet af osteopontin er valgt fra gruppen bestående af YPDAVATWLNPDPSQKQNLLAPQNAVSSEETNDFKQETLPSK (SEQ ID NO:8) og KYPDAVATWLNPDPSQKQNLLAPQTLPSK (SEQ ID NO:9).
26. Fremgangsmåden ifølge kravene 22 til 25, hvor sygdomsscoren beregnes af en analyse valgt fra gruppen bestående af ridge regressionsanalyse, faktoranalyse, diskriminant funktionsanalyse, og logistisk regressionsanalyse.
27. Isoleret antistof som specifikt binder til et peptid valgt fra gruppen bestående af: WSLGSPSGEVSHPRKT (SEQ ID NO:l) og MGWSLGSPSGEVSHPRKT (SEQ ID NO:2).
28. Kit til at diagnosticere diabetisk nefropati, omfattende et antistofsom er i stand til at binde til et fragment af alpha-2-HS-glycoprotein valgt fra gruppen bestående af WSLGSPSGEVSHPRKT (SEQ ID NO:l) og MGWSLGSPSGEVSHPRKT (SEQ ID NO:2).
29. Kittet ifølge krav 28, endvidere omfattende et antistof, som er i stand til at binde til et fragment af alpha-1 antitrypsin valgt fra gruppen bestående af KGKWERPFEVKDTEEEDF (SEQ ID NO:3), MIEQNTKSPLFMGKWNPTQK (SEQ ID NO:4), EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAE (SEQ ID NO:5), og EDPQGDAAQKTDTSΗHDQDHPTFNKITPNLAEFA (SEQ ID NO:6);
30. Kittet ifølge krav 28 eller 29, endvidere omfattende et antistof, som er i stand til at binde til GQEHFAHLLILRDTKTYMLAFDVNDEKNWGLS (SEQ ID N0:7).
31. Kittet ifølge kravene 28 til 30, endvidere omfattende et antistof, som er i stand til at binde til et fragment af osteopontin valgt fra gruppen bestående af YPDAVATWLNPDPSQKQNLLAPQNAVSSEETNDFKQETLPSK (SEQ ID NO:8) og KYPDAVATWLNPDPSQKQNLLAPQTLPSK (SEQ ID NO:9).
32. Kittet ifølge kravene 28 til 31, hvor antistofferne er hele immunoglobulin-molekyler.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14777809P | 2009-01-28 | 2009-01-28 | |
| PCT/CA2010/000097 WO2010085879A1 (en) | 2009-01-28 | 2010-01-27 | Urine and serum biomarkers associated with diabetic nephropathy |
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| RU2596486C2 (ru) * | 2010-09-21 | 2016-09-10 | Протеомикс Интернешнл Пти Лтд | Биомаркеры, ассоциированные с предиабетом, диабетом и связанными с диабетом состояниями |
| JP5714285B2 (ja) * | 2010-09-29 | 2015-05-07 | 株式会社プロトセラ | 妊娠高血圧症候群マーカーおよびそれを用いた診断 |
| ES2656150T3 (es) * | 2011-11-14 | 2018-02-23 | Universitätsklinikum Jena | Diagnóstico de la sepsis y del síndrome de respuesta inflamatoria sistémica |
| WO2013115283A1 (ja) * | 2012-01-31 | 2013-08-08 | 味の素株式会社 | 早期腎症の評価方法、早期腎症評価装置、早期腎症評価方法、早期腎症評価プログラム、早期腎症評価システムおよび情報通信端末装置 |
| WO2013122976A1 (en) * | 2012-02-13 | 2013-08-22 | New York University | Osteopontin isoform a inhibitors and methods of use |
| GB201203938D0 (en) * | 2012-03-06 | 2012-04-18 | Binding Site Group The Ltd | Assay system |
| US10018591B2 (en) | 2012-06-11 | 2018-07-10 | Preventage Healthcare, Llc | Methods for improving diabetes management |
| CA2929444C (en) * | 2013-11-04 | 2023-12-19 | F. Hoffmann-La Roche Ag | Biomarkers and methods for progression prediction for chronic kidney disease |
| CN103804484B (zh) * | 2014-01-24 | 2016-03-16 | 南京必优康生物技术有限公司 | 一种网红细胞生长因子及其制备方法和应用 |
| CN105572355B (zh) * | 2015-03-13 | 2018-04-13 | 中国医学科学院肿瘤医院 | 检测食管癌的生物标志物 |
| EP3935581A4 (en) | 2019-03-04 | 2022-11-30 | Iocurrents, Inc. | DATA COMPRESSION AND COMMUNICATION USING MACHINE LEARNING |
| CN114487431A (zh) * | 2020-11-12 | 2022-05-13 | 首都医科大学附属北京世纪坛医院 | 尿液α-2-HS-糖蛋白及其多肽片段在妊娠糖尿病中的应用 |
| CN113687083B (zh) * | 2021-08-20 | 2023-11-28 | 天津中医药大学 | 一种基于深度学习的糖尿病肾病早期预测方法及系统 |
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| US20050266467A1 (en) * | 2004-05-19 | 2005-12-01 | Ppd Biomarker Discovery Sciences, Llc | Biomarkers for multiple sclerosis and methods of use thereof |
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| WO2007110230A2 (en) * | 2006-03-27 | 2007-10-04 | Institut Pasteur | Secreted proteins as early markers and drug targets for autoimmunity, tumorigenesis and infections |
| AU2007284651B2 (en) * | 2006-08-09 | 2014-03-20 | Institute For Systems Biology | Organ-specific proteins and methods of their use |
| WO2008092214A1 (en) | 2007-02-02 | 2008-08-07 | Minomic International Limited | Biomarkers for diabetes |
| CN103399155A (zh) | 2007-03-26 | 2013-11-20 | 诺瓦提斯公司 | 用于监测肾功能的预测性的肾安全性生物标志物和生物标志物标签 |
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| DK2391653T3 (da) * | 2009-01-28 | 2015-02-09 | Ind Tech Res Inst | Biomarkører associeret med nefropati |
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