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Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection

Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. Thi...

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Autores principales: Freue, Gabriela V. Cohen, Sasaki, Mayu, Meredith, Anna, Günther, Oliver P., Bergman, Axel, Takhar, Mandeep, Mui, Alice, Balshaw, Robert F., Ng, Raymond T., Opushneva, Nina, Hollander, Zsuzsanna, Li, Guiyun, Borchers, Christoph H., Wilson-McManus, Janet, McManus, Bruce M., Keown, Paul A., McMaster, W. Robert
Formato: Texto
Lenguaje:English
Publicado: The American Society for Biochemistry and Molecular Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938106/
https://www.ncbi.nlm.nih.gov/pubmed/20501940
http://dx.doi.org/10.1074/mcp.M110.000554
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author Freue, Gabriela V. Cohen
Sasaki, Mayu
Meredith, Anna
Günther, Oliver P.
Bergman, Axel
Takhar, Mandeep
Mui, Alice
Balshaw, Robert F.
Ng, Raymond T.
Opushneva, Nina
Hollander, Zsuzsanna
Li, Guiyun
Borchers, Christoph H.
Wilson-McManus, Janet
McManus, Bruce M.
Keown, Paul A.
McMaster, W. Robert
author_facet Freue, Gabriela V. Cohen
Sasaki, Mayu
Meredith, Anna
Günther, Oliver P.
Bergman, Axel
Takhar, Mandeep
Mui, Alice
Balshaw, Robert F.
Ng, Raymond T.
Opushneva, Nina
Hollander, Zsuzsanna
Li, Guiyun
Borchers, Christoph H.
Wilson-McManus, Janet
McManus, Bruce M.
Keown, Paul A.
McMaster, W. Robert
author_sort Freue, Gabriela V. Cohen
collection PubMed
description Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change ≥1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and β(2)-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and controls throughout the period of quiescent follow-up. Results were validated using ELISA where possible, and initial cross-validation estimated a sensitivity of 80% and specificity of 90% for classification of BCAR based on a four-protein ELISA classifier. This study provides evidence that protein concentrations in plasma may provide a relevant measure for the occurrence of BCAR and offers a potential tool for immunologic monitoring.
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spelling pubmed-29381062010-09-17 Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection Freue, Gabriela V. Cohen Sasaki, Mayu Meredith, Anna Günther, Oliver P. Bergman, Axel Takhar, Mandeep Mui, Alice Balshaw, Robert F. Ng, Raymond T. Opushneva, Nina Hollander, Zsuzsanna Li, Guiyun Borchers, Christoph H. Wilson-McManus, Janet McManus, Bruce M. Keown, Paul A. McMaster, W. Robert Mol Cell Proteomics Research Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change ≥1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and β(2)-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and controls throughout the period of quiescent follow-up. Results were validated using ELISA where possible, and initial cross-validation estimated a sensitivity of 80% and specificity of 90% for classification of BCAR based on a four-protein ELISA classifier. This study provides evidence that protein concentrations in plasma may provide a relevant measure for the occurrence of BCAR and offers a potential tool for immunologic monitoring. The American Society for Biochemistry and Molecular Biology 2010-09 2010-05-25 /pmc/articles/PMC2938106/ /pubmed/20501940 http://dx.doi.org/10.1074/mcp.M110.000554 Text en © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
spellingShingle Research
Freue, Gabriela V. Cohen
Sasaki, Mayu
Meredith, Anna
Günther, Oliver P.
Bergman, Axel
Takhar, Mandeep
Mui, Alice
Balshaw, Robert F.
Ng, Raymond T.
Opushneva, Nina
Hollander, Zsuzsanna
Li, Guiyun
Borchers, Christoph H.
Wilson-McManus, Janet
McManus, Bruce M.
Keown, Paul A.
McMaster, W. Robert
Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection
title Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection
title_full Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection
title_fullStr Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection
title_full_unstemmed Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection
title_short Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection
title_sort proteomic signatures in plasma during early acute renal allograft rejection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938106/
https://www.ncbi.nlm.nih.gov/pubmed/20501940
http://dx.doi.org/10.1074/mcp.M110.000554
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