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Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis

INTRODUCTION: Anti-TNF therapies have revolutionized the treatment of rheumatoid arthritis (RA), a common systemic autoimmune disease involving destruction of the synovial joints. However, in the practice of rheumatology approximately one-third of patients demonstrate no clinical improvement in resp...

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Autores principales: Hueber, Wolfgang, Tomooka, Beren H, Batliwalla, Franak, Li, Wentian, Monach, Paul A, Tibshirani, Robert J, Van Vollenhoven, Ronald F, Lampa, Jon, Saito, Kazuyoshi, Tanaka, Yoshiya, Genovese, Mark C, Klareskog, Lars, Gregersen, Peter K, Robinson, William H
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714123/
https://www.ncbi.nlm.nih.gov/pubmed/19460157
http://dx.doi.org/10.1186/ar2706
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author Hueber, Wolfgang
Tomooka, Beren H
Batliwalla, Franak
Li, Wentian
Monach, Paul A
Tibshirani, Robert J
Van Vollenhoven, Ronald F
Lampa, Jon
Saito, Kazuyoshi
Tanaka, Yoshiya
Genovese, Mark C
Klareskog, Lars
Gregersen, Peter K
Robinson, William H
author_facet Hueber, Wolfgang
Tomooka, Beren H
Batliwalla, Franak
Li, Wentian
Monach, Paul A
Tibshirani, Robert J
Van Vollenhoven, Ronald F
Lampa, Jon
Saito, Kazuyoshi
Tanaka, Yoshiya
Genovese, Mark C
Klareskog, Lars
Gregersen, Peter K
Robinson, William H
author_sort Hueber, Wolfgang
collection PubMed
description INTRODUCTION: Anti-TNF therapies have revolutionized the treatment of rheumatoid arthritis (RA), a common systemic autoimmune disease involving destruction of the synovial joints. However, in the practice of rheumatology approximately one-third of patients demonstrate no clinical improvement in response to treatment with anti-TNF therapies, while another third demonstrate a partial response, and one-third an excellent and sustained response. Since no clinical or laboratory tests are available to predict response to anti-TNF therapies, great need exists for predictive biomarkers. METHODS: Here we present a multi-step proteomics approach using arthritis antigen arrays, a multiplex cytokine assay, and conventional ELISA, with the objective to identify a biomarker signature in three ethnically diverse cohorts of RA patients treated with the anti-TNF therapy etanercept. RESULTS: We identified a 24-biomarker signature that enabled prediction of a positive clinical response to etanercept in all three cohorts (positive predictive values 58 to 72%; negative predictive values 63 to 78%). CONCLUSIONS: We identified a multi-parameter protein biomarker that enables pretreatment classification and prediction of etanercept responders, and tested this biomarker using three independent cohorts of RA patients. Although further validation in prospective and larger cohorts is needed, our observations demonstrate that multiplex characterization of autoantibodies and cytokines provides clinical utility for predicting response to the anti-TNF therapy etanercept in RA patients.
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spelling pubmed-27141232009-07-22 Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis Hueber, Wolfgang Tomooka, Beren H Batliwalla, Franak Li, Wentian Monach, Paul A Tibshirani, Robert J Van Vollenhoven, Ronald F Lampa, Jon Saito, Kazuyoshi Tanaka, Yoshiya Genovese, Mark C Klareskog, Lars Gregersen, Peter K Robinson, William H Arthritis Res Ther Research Article INTRODUCTION: Anti-TNF therapies have revolutionized the treatment of rheumatoid arthritis (RA), a common systemic autoimmune disease involving destruction of the synovial joints. However, in the practice of rheumatology approximately one-third of patients demonstrate no clinical improvement in response to treatment with anti-TNF therapies, while another third demonstrate a partial response, and one-third an excellent and sustained response. Since no clinical or laboratory tests are available to predict response to anti-TNF therapies, great need exists for predictive biomarkers. METHODS: Here we present a multi-step proteomics approach using arthritis antigen arrays, a multiplex cytokine assay, and conventional ELISA, with the objective to identify a biomarker signature in three ethnically diverse cohorts of RA patients treated with the anti-TNF therapy etanercept. RESULTS: We identified a 24-biomarker signature that enabled prediction of a positive clinical response to etanercept in all three cohorts (positive predictive values 58 to 72%; negative predictive values 63 to 78%). CONCLUSIONS: We identified a multi-parameter protein biomarker that enables pretreatment classification and prediction of etanercept responders, and tested this biomarker using three independent cohorts of RA patients. Although further validation in prospective and larger cohorts is needed, our observations demonstrate that multiplex characterization of autoantibodies and cytokines provides clinical utility for predicting response to the anti-TNF therapy etanercept in RA patients. BioMed Central 2009 2009-05-21 /pmc/articles/PMC2714123/ /pubmed/19460157 http://dx.doi.org/10.1186/ar2706 Text en Copyright © 2009 Hueber et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hueber, Wolfgang
Tomooka, Beren H
Batliwalla, Franak
Li, Wentian
Monach, Paul A
Tibshirani, Robert J
Van Vollenhoven, Ronald F
Lampa, Jon
Saito, Kazuyoshi
Tanaka, Yoshiya
Genovese, Mark C
Klareskog, Lars
Gregersen, Peter K
Robinson, William H
Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis
title Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis
title_full Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis
title_fullStr Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis
title_full_unstemmed Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis
title_short Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis
title_sort blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714123/
https://www.ncbi.nlm.nih.gov/pubmed/19460157
http://dx.doi.org/10.1186/ar2706
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