Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Gene expression profiles were examined in freshly isolated peripheral blood mononuclear cells (PBMC) from two independent cohorts (training and test sets) of glucocorticoid (GC)-sensitive (...
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Online Access: | http://hdl.handle.net/2336/57933 https://doi.org/10.1073/pnas.0409904102 |
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ftlandspitaliuni:oai:www.hirsla.lsh.is:2336/57933 2023-05-15T16:52:20+02:00 Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients Hakonarson, Hakon Bjornsdottir, Unnur S Halapi, Eva Bradfield, Jonathan Zink, Florian Mouy, Magali Helgadottir, Hildur Gudmundsdottir, Asta S Andrason, Hjalti Adalsteinsdottir, Asdis E Kristjansson, Kristleifur Birkisson, Illugi Arnason, Thor Andresdottir, Margret Gislason, David Gislason, Thorarinn Gulcher, Jeffrey R Stefansson, Kari deCODE genetics, Inc., Sturlugata 8, IS-101 Reykjavik, Iceland. hakonh@decode.is 2009-03-30 http://hdl.handle.net/2336/57933 https://doi.org/10.1073/pnas.0409904102 en eng National Academy of Sciences http://dx.doi.org/10.1073/pnas.0409904102 Proc. Natl. Acad. Sci. U.S.A. 2005, 102(41):14789-94 0027-8424 16203992 doi:10.1073/pnas.0409904102 http://hdl.handle.net/2336/57933 Proceedings of the National Academy of Sciences of the United States of America Adult Aged Asthma Cohort Studies Female Gene Expression Profiling Gene Expression Regulation Glucocorticoids Humans Iceland Interleukin-1 Leukocytes Mononuclear Male Middle Aged Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Article 2009 ftlandspitaliuni https://doi.org/10.1073/pnas.0409904102 2022-05-29T08:21:18Z To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Gene expression profiles were examined in freshly isolated peripheral blood mononuclear cells (PBMC) from two independent cohorts (training and test sets) of glucocorticoid (GC)-sensitive (n = 64) and GC-resistant (n = 42) asthma patients in search of genes that accurately predict responders and nonresponders to inhaled corticosteroids. A total of 11,812 genes were examined with high-density oligonucleotide microarrays in both resting PBMC (106 patients) and cells treated in vitro with IL-1beta and TNF-alpha combined (88 patients), with or without GC. A total of 5,011 genes were expressed at significant levels in the PBMC, and 1,334 of those were notably up-regulated or down-regulated by IL-1beta/TNF-alpha treatment. The expression changes of 923 genes were significantly reversed in GC responders in the presence of GC. The expression pattern of 15 of these 923 genes that most accurately separated GC responders (n = 26) from the nonresponders (n = 18) in the training set, based on the weighted voting algorithm, predicted the independent test set of equal size with 84% accuracy. The expression accuracy of these genes was confirmed by real-time-quantitative PCR, wherein 11 of the 15 genes predicted GC sensitivity at baseline with 84% accuracy, with one gene predicting at 81% in an independent cohort of 79 patients. We conclude that we have uncovered gene expression profiles in PBMC that predict clinical response to inhaled GC therapy with meaningful accuracy. Upon validation in an independent study, these results support the development of a diagnostic test to guide GC therapy in asthma patients. Article in Journal/Newspaper Iceland Hirsla - Landspítali University Hospital research archive Proceedings of the National Academy of Sciences 102 41 14789 14794 |
institution |
Open Polar |
collection |
Hirsla - Landspítali University Hospital research archive |
op_collection_id |
ftlandspitaliuni |
language |
English |
topic |
Adult Aged Asthma Cohort Studies Female Gene Expression Profiling Gene Expression Regulation Glucocorticoids Humans Iceland Interleukin-1 Leukocytes Mononuclear Male Middle Aged Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha |
spellingShingle |
Adult Aged Asthma Cohort Studies Female Gene Expression Profiling Gene Expression Regulation Glucocorticoids Humans Iceland Interleukin-1 Leukocytes Mononuclear Male Middle Aged Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Hakonarson, Hakon Bjornsdottir, Unnur S Halapi, Eva Bradfield, Jonathan Zink, Florian Mouy, Magali Helgadottir, Hildur Gudmundsdottir, Asta S Andrason, Hjalti Adalsteinsdottir, Asdis E Kristjansson, Kristleifur Birkisson, Illugi Arnason, Thor Andresdottir, Margret Gislason, David Gislason, Thorarinn Gulcher, Jeffrey R Stefansson, Kari Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients |
topic_facet |
Adult Aged Asthma Cohort Studies Female Gene Expression Profiling Gene Expression Regulation Glucocorticoids Humans Iceland Interleukin-1 Leukocytes Mononuclear Male Middle Aged Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha |
description |
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Gene expression profiles were examined in freshly isolated peripheral blood mononuclear cells (PBMC) from two independent cohorts (training and test sets) of glucocorticoid (GC)-sensitive (n = 64) and GC-resistant (n = 42) asthma patients in search of genes that accurately predict responders and nonresponders to inhaled corticosteroids. A total of 11,812 genes were examined with high-density oligonucleotide microarrays in both resting PBMC (106 patients) and cells treated in vitro with IL-1beta and TNF-alpha combined (88 patients), with or without GC. A total of 5,011 genes were expressed at significant levels in the PBMC, and 1,334 of those were notably up-regulated or down-regulated by IL-1beta/TNF-alpha treatment. The expression changes of 923 genes were significantly reversed in GC responders in the presence of GC. The expression pattern of 15 of these 923 genes that most accurately separated GC responders (n = 26) from the nonresponders (n = 18) in the training set, based on the weighted voting algorithm, predicted the independent test set of equal size with 84% accuracy. The expression accuracy of these genes was confirmed by real-time-quantitative PCR, wherein 11 of the 15 genes predicted GC sensitivity at baseline with 84% accuracy, with one gene predicting at 81% in an independent cohort of 79 patients. We conclude that we have uncovered gene expression profiles in PBMC that predict clinical response to inhaled GC therapy with meaningful accuracy. Upon validation in an independent study, these results support the development of a diagnostic test to guide GC therapy in asthma patients. |
author2 |
deCODE genetics, Inc., Sturlugata 8, IS-101 Reykjavik, Iceland. hakonh@decode.is |
format |
Article in Journal/Newspaper |
author |
Hakonarson, Hakon Bjornsdottir, Unnur S Halapi, Eva Bradfield, Jonathan Zink, Florian Mouy, Magali Helgadottir, Hildur Gudmundsdottir, Asta S Andrason, Hjalti Adalsteinsdottir, Asdis E Kristjansson, Kristleifur Birkisson, Illugi Arnason, Thor Andresdottir, Margret Gislason, David Gislason, Thorarinn Gulcher, Jeffrey R Stefansson, Kari |
author_facet |
Hakonarson, Hakon Bjornsdottir, Unnur S Halapi, Eva Bradfield, Jonathan Zink, Florian Mouy, Magali Helgadottir, Hildur Gudmundsdottir, Asta S Andrason, Hjalti Adalsteinsdottir, Asdis E Kristjansson, Kristleifur Birkisson, Illugi Arnason, Thor Andresdottir, Margret Gislason, David Gislason, Thorarinn Gulcher, Jeffrey R Stefansson, Kari |
author_sort |
Hakonarson, Hakon |
title |
Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients |
title_short |
Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients |
title_full |
Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients |
title_fullStr |
Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients |
title_full_unstemmed |
Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients |
title_sort |
profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients |
publisher |
National Academy of Sciences |
publishDate |
2009 |
url |
http://hdl.handle.net/2336/57933 https://doi.org/10.1073/pnas.0409904102 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://dx.doi.org/10.1073/pnas.0409904102 Proc. Natl. Acad. Sci. U.S.A. 2005, 102(41):14789-94 0027-8424 16203992 doi:10.1073/pnas.0409904102 http://hdl.handle.net/2336/57933 Proceedings of the National Academy of Sciences of the United States of America |
op_doi |
https://doi.org/10.1073/pnas.0409904102 |
container_title |
Proceedings of the National Academy of Sciences |
container_volume |
102 |
container_issue |
41 |
container_start_page |
14789 |
op_container_end_page |
14794 |
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1766042478492778496 |