Identification of candidate IgG biomarkers for Alzheimer's disease via combinatorial library screening.

Identification of candidate IgG biomarkers for Alzheimer's disease via combinatorial library screening.
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DOI:
10.1016/j.cell.2010.11.054
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发表时间:
2011-01-07
期刊:
影响因子:
64.5
通讯作者:
Kodadek T
Kodadek T
中科院分区:
生物学1区
文献类型:
--
作者:
Reddy MM;Wilson R;Wilson J;Connell S;Gocke A;Hynan L;German D;Kodadek T

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适应性免疫系统被认为是蛋白质生物标记物的丰富来源,但对许多疾病来说,诊断有用的抗体仍然未知。这在一定程度上是因为在许多疾病中触发免疫反应的抗原仍然未知。我们在这里提出了一种一般的和无偏见的方法来鉴定诊断有用的抗体,避免了对抗原鉴定的要求。该方法涉及对非天然合成分子的组合文库与从病例和对照中获得的血清样本进行比较筛选。从病例样本中保留比对照多得多的免疫球蛋白抗体的分子被识别出来,随后作为诊断有用抗体的捕获剂进行测试。使用多发性硬化症的小鼠模型,并通过识别阿尔茨海默病的两个候选免疫球蛋白生物标志物,证明了该方法的实用性。
The adaptive immune system is thought to be a rich source of protein biomarkers, but diagnostically useful antibodies remain unknown for a large number of diseases. This is, in part, because the antigens that trigger an immune response in many diseases remain unknown. We present here a general and unbiased approach to the identification of diagnostically useful antibodies that avoids the requirement for antigen identification. This method involves the comparative screening of combinatorial libraries of unnatural, synthetic molecules against serum samples obtained from cases and controls. Molecules that retain far more IgG antibodies from the case samples than the controls are identified and subsequently tested as capture agents for diagnostically useful antibodies. The utility of this method is demonstrated using a mouse model for multiple sclerosis and via the identification of two candidate IgG biomarkers for Alzheimer's Disease.
DOI: 10.1001/archgenpsychiatry.2010.78
发表时间: 2010-07
影响因子: --
作者:
Thambisetty, Madhav;Simmons, Andrew;Velayudhan, Latha;Hye, Abdul;Campbell, James;Zhang, Yi;Wahlund, Lars-Olof;Westman, Eric;Kinsey, Anna;Guntert, Andreas;Proitsi, Petroula;Powell, John;Causevic, Mirsada;Killick, Richard;Lunnon, Katie;Lynham, Steven;Broadstock, Martin;Choudhry, Fahd;Howlett, David R.;Williams, Robert J.;Sharp, Sally I.;Mitchelmore, Cathy;Tunnard, Catherine;Leung, Rufina;Foy, Catherine;O'Brien, Darragh;Breen, Gerome;Furney, Simon J.;Ward, Malcolm;Kloszewska, Iwona;Mecocci, Patrizia;Soininen, Hilkka;Tsolaki, Magda;Vellas, Bruno;Hodges, Angela;Murphy, Declan G. M.;Parkins, Sue;Richardson, Jill C.;Resnick, Susan M.;Ferrucci, Luigi;Wong, Dean F.;Zhou, Yun;Muehlboeck, Sebastian;Evans, Alan;Francis, Paul T.;Spenger, Christian;Lovestone, Simon
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发表时间: 2002-03-01
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发表时间: 1992-10-15
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通讯作者: BARTLETT, PA
DOI: 10.1517/14712590902870386
发表时间: 2009-04
影响因子: 4.6
作者:
Knittelfelder R;Riemer AB;Jensen-Jarolim E
通讯作者: Jensen-Jarolim E
DOI: 10.1038/nm1344
发表时间: 2006-01-01
期刊: NATURE MEDICINE
影响因子: 82.9
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