Cargando…

Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease

BACKGROUND: Biological therapies have been introduced for the treatment of chronic inflammatory diseases including rheumatoid arthritis (RA) and Crohn's disease (CD). The efficacy of biologics differs from patient to patient. Moreover these therapies are rather expensive, therefore treatment of...

Descripción completa

Detalles Bibliográficos
Autores principales: Mesko, Bertalan, Poliska, Szilard, Váncsa, Andrea, Szekanecz, Zoltan, Palatka, Karoly, Hollo, Zsolt, Horvath, Attila, Steiner, Laszlo, Zahuczky, Gabor, Podani, Janos, Nagy, and Laszlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064310/
https://www.ncbi.nlm.nih.gov/pubmed/23809696
http://dx.doi.org/10.1186/gm463
_version_ 1782321937146445824
author Mesko, Bertalan
Poliska, Szilard
Váncsa, Andrea
Szekanecz, Zoltan
Palatka, Karoly
Hollo, Zsolt
Horvath, Attila
Steiner, Laszlo
Zahuczky, Gabor
Podani, Janos
Nagy, and Laszlo
author_facet Mesko, Bertalan
Poliska, Szilard
Váncsa, Andrea
Szekanecz, Zoltan
Palatka, Karoly
Hollo, Zsolt
Horvath, Attila
Steiner, Laszlo
Zahuczky, Gabor
Podani, Janos
Nagy, and Laszlo
author_sort Mesko, Bertalan
collection PubMed
description BACKGROUND: Biological therapies have been introduced for the treatment of chronic inflammatory diseases including rheumatoid arthritis (RA) and Crohn's disease (CD). The efficacy of biologics differs from patient to patient. Moreover these therapies are rather expensive, therefore treatment of primary non-responders should be avoided. METHOD: We addressed this issue by combining gene expression profiling and biostatistical approaches. We performed peripheral blood global gene expression profiling in order to filter the genome for target genes in cohorts of 20 CD and 19 RA patients. Then RT-quantitative PCR validation was performed, followed by multivariate analyses of genes in independent cohorts of 20 CD and 15 RA patients, in order to identify sets ofinterrelated genes that can separate responders from non-responders to the humanized chimeric anti-TNFalpha antibody infliximab at baseline. RESULTS: Gene panels separating responders from non-responders were identified using leave-one-out cross-validation test, and a pool of genes that should be tested on larger cohorts was created in both conditions. CONCLUSIONS: Our data show that peripheral blood gene expression profiles are suitable for determining gene panels with high discriminatory power to differentiate responders from non-responders in infliximab therapy at baseline in CD and RA, which could be cross-validated successfully. Biostatistical analysis of peripheral blood gene expression data leads to the identification of gene panels that can help predict responsiveness of therapy and support the clinical decision-making process.
format Online
Article
Text
id pubmed-4064310
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-40643102014-06-21 Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease Mesko, Bertalan Poliska, Szilard Váncsa, Andrea Szekanecz, Zoltan Palatka, Karoly Hollo, Zsolt Horvath, Attila Steiner, Laszlo Zahuczky, Gabor Podani, Janos Nagy, and Laszlo Genome Med Research BACKGROUND: Biological therapies have been introduced for the treatment of chronic inflammatory diseases including rheumatoid arthritis (RA) and Crohn's disease (CD). The efficacy of biologics differs from patient to patient. Moreover these therapies are rather expensive, therefore treatment of primary non-responders should be avoided. METHOD: We addressed this issue by combining gene expression profiling and biostatistical approaches. We performed peripheral blood global gene expression profiling in order to filter the genome for target genes in cohorts of 20 CD and 19 RA patients. Then RT-quantitative PCR validation was performed, followed by multivariate analyses of genes in independent cohorts of 20 CD and 15 RA patients, in order to identify sets ofinterrelated genes that can separate responders from non-responders to the humanized chimeric anti-TNFalpha antibody infliximab at baseline. RESULTS: Gene panels separating responders from non-responders were identified using leave-one-out cross-validation test, and a pool of genes that should be tested on larger cohorts was created in both conditions. CONCLUSIONS: Our data show that peripheral blood gene expression profiles are suitable for determining gene panels with high discriminatory power to differentiate responders from non-responders in infliximab therapy at baseline in CD and RA, which could be cross-validated successfully. Biostatistical analysis of peripheral blood gene expression data leads to the identification of gene panels that can help predict responsiveness of therapy and support the clinical decision-making process. BioMed Central 2013-06-28 /pmc/articles/PMC4064310/ /pubmed/23809696 http://dx.doi.org/10.1186/gm463 Text en Copyright © 2013 Mesko 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
Mesko, Bertalan
Poliska, Szilard
Váncsa, Andrea
Szekanecz, Zoltan
Palatka, Karoly
Hollo, Zsolt
Horvath, Attila
Steiner, Laszlo
Zahuczky, Gabor
Podani, Janos
Nagy, and Laszlo
Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease
title Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease
title_full Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease
title_fullStr Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease
title_full_unstemmed Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease
title_short Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease
title_sort peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and crohn's disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064310/
https://www.ncbi.nlm.nih.gov/pubmed/23809696
http://dx.doi.org/10.1186/gm463
work_keys_str_mv AT meskobertalan peripheralbloodderivedgenepanelspredictresponsetoinfliximabinrheumatoidarthritisandcrohnsdisease
AT poliskaszilard peripheralbloodderivedgenepanelspredictresponsetoinfliximabinrheumatoidarthritisandcrohnsdisease
AT vancsaandrea peripheralbloodderivedgenepanelspredictresponsetoinfliximabinrheumatoidarthritisandcrohnsdisease
AT szekaneczzoltan peripheralbloodderivedgenepanelspredictresponsetoinfliximabinrheumatoidarthritisandcrohnsdisease
AT palatkakaroly peripheralbloodderivedgenepanelspredictresponsetoinfliximabinrheumatoidarthritisandcrohnsdisease
AT hollozsolt peripheralbloodderivedgenepanelspredictresponsetoinfliximabinrheumatoidarthritisandcrohnsdisease
AT horvathattila peripheralbloodderivedgenepanelspredictresponsetoinfliximabinrheumatoidarthritisandcrohnsdisease
AT steinerlaszlo peripheralbloodderivedgenepanelspredictresponsetoinfliximabinrheumatoidarthritisandcrohnsdisease
AT zahuczkygabor peripheralbloodderivedgenepanelspredictresponsetoinfliximabinrheumatoidarthritisandcrohnsdisease
AT podanijanos peripheralbloodderivedgenepanelspredictresponsetoinfliximabinrheumatoidarthritisandcrohnsdisease
AT nagyandlaszlo peripheralbloodderivedgenepanelspredictresponsetoinfliximabinrheumatoidarthritisandcrohnsdisease