Comprehensive Urinomic Identification of Protein Alternatives to Creatinine Normalization for Diagnostic Assessment of Lupus Nephritis.
Comprehensive Urinomic Identification of Protein Alternatives to Creatinine Normalization for Diagnostic Assessment of Lupus Nephritis.
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DOI：
10.3389/fimmu.2022.853778
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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目前用于尿液生物标志物标准化的金标准肌酐对转化为护理点提出了挑战，因为肌酐的抗体很难开发，目前可用的肌酐配体对于这一目的来说是次优的。因此，显然需要肌酸酐的蛋白质替代品。为了满足这一需求，狼疮肾炎被选为一种模型疾病，其中尿蛋白评估是诊断所必需的。对健康和狼疮肾炎尿液中的1129种蛋白质进行了全面的蛋白质组学筛选，以确定替代肌酐的尿液生物标志物正常化的蛋白质。尿蛋白与肌酐密切相关，但不随疾病变化，在一个独立的狼疮性肾炎受试者队列中通过ELISA进一步验证。综合蛋白质组学筛查确定了14种与尿肌酐显著相关的尿蛋白，但在SLE和对照组之间没有显著差异。在选择用于ELISA验证的前5种蛋白中，尿HVEM和RELT在独立队列中再次显示出与尿肌酐的显著相关性。在区分活动性狼疮性肾炎和非活动性SLE患者时，使用尿HVEM使狼疮性肾炎候选生物标志物ALCAM正常化显示出与肌酐正常化相当的诊断能力。尿HVEM作为一种蛋白质替代肌酐用于生物标志物标准化的发现，在基于抗体的护理点诊断工程中用于监测狼疮性肾炎的进展。
The current gold standard used for urine biomarker normalization, creatinine, poses a challenge to translate to the point of care because antibodies to creatinine are difficult to develop and currently available ligands to creatinine are sub-optimal for this purpose. Hence, protein alternatives to creatinine are clearly needed. To address this need, lupus nephritis was selected as a model disease where urine protein assessment is required for diagnosis. A comprehensive proteomic screen of 1129 proteins in healthy and lupus nephritis urine was executed to identify protein alternatives to creatinine for the normalization of urine biomarkers. Urinary proteins that correlated well with creatinine but did not vary with disease were further validated by ELISA in an independent cohort of lupus nephritis subjects. The comprehensive proteomic screen identified 14 urine proteins that correlated significantly with urine creatinine but did not differ significantly between SLE and controls. Of the top five proteins selected for ELISA validation, urine HVEM and RELT once again showed significant correlation with urine creatinine in independent cohorts. Normalizing a lupus nephritis biomarker candidate ALCAM using urinary HVEM demonstrated comparable diagnostic ability to creatinine normalization when distinguishing active lupus nephritis from inactive SLE patients. The discovery of urine HVEM as a protein alternative to creatinine for biomarker normalization has applications in the engineering of antibody-based point of care diagnostics for monitoring lupus nephritis progression.
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DOI：
10.1038/mtna.2014.49
发表时间：
2014-10-07
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
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影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
--
作者：
Petri, Michelle;Orbai, Ana-Maria;Alarcon, Graciela S.;Gordon, Caroline;Merrill, Joan T.;Fortin, Paul R.;Bruce, Ian N.;Isenberg, David;Wallace, Daniel J.;Nived, Ola;Sturfelt, Gunnar;Ramsey-Goldman, Rosalind;Bae, Sang-Cheol;Hanly, John G.;Sanchez-Guerrero, Jorge;Clarke, Ann;Aranow, Cynthia;Manzi, Susan;Urowitz, Murray;Gladman, Dafna;Kalunian, Kenneth;Costner, Melissa;Werth, Victoria P.;Zoma, Asad;Bernatsky, Sasha;Ruiz-Irastorza, Guillermo;Khamashta, Munther A.;Jacobsen, Soren;Buyon, Jill P.;Maddison, Peter;Dooley, Mary Anne;van vollenhoven, Ronald F.;Ginzler, Ellen;Stoll, Thomas;Peschken, Christine;Jorizzo, Joseph L.;Callen, Jeffrey P.;Lim, S. Sam;Fessler, Barri J.;Inanc, Murat;Kamen, Diane L.;Rahman, Anisur;Steinsson, Kristjan;Franks, Andrew G., Jr.;Sigler, Lisa;Hameed, Suhail;Fang, Hong;Ngoc Pham;Brey, Robin;Weisman, Michael H.;McGwin, Gerald, Jr.;Magder, Laurence S.
通讯作者：
Magder, Laurence S.
影响因子：
2
作者：
Dams, R;Murphy, CM;Huestis, MA
通讯作者：
Huestis, MA
影响因子：
3.7
作者：
Tsang, Julia Y. S.;Chan, Kit-Wing;Tse, Gary M.
通讯作者：
Tse, Gary M.