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Immunosuppressant exposure confounds gene expression analysis in systemic lupus erythematosus
OBJECTIVES: The analysis of gene module expression in SLE is emerging as a tool to identify active biological pathways, with the aim of developing targeted therapies for subsets of patients. Detailed information on the effect of immunosuppressants on gene module expression is lacking. We aimed to ex...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9430375/ https://www.ncbi.nlm.nih.gov/pubmed/36059457 http://dx.doi.org/10.3389/fimmu.2022.964263 |
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author | Northcott, Melissa Gearing, Linden J. Bonin, Julie Koelmeyer, Rachel Hoi, Alberta Hertzog, Paul J. Morand, Eric F. |
author_facet | Northcott, Melissa Gearing, Linden J. Bonin, Julie Koelmeyer, Rachel Hoi, Alberta Hertzog, Paul J. Morand, Eric F. |
author_sort | Northcott, Melissa |
collection | PubMed |
description | OBJECTIVES: The analysis of gene module expression in SLE is emerging as a tool to identify active biological pathways, with the aim of developing targeted therapies for subsets of patients. Detailed information on the effect of immunosuppressants on gene module expression is lacking. We aimed to examine the impact of medication exposure on gene module expression. METHODS: A set of commercially available disease-relevant gene modules were measured in 730 whole blood samples from a dedicated lupus clinic on whom prospectively collected, contemporaneous clinical data including medication exposure were available. RESULTS: Compared to heathy controls, SLE patients showed over-expression of IFN and under-expression of B cell, T cell and pDC modules. Neutrophil module over-expression and under-expression of B and T cell modules were observed in patients with active lupus nephritis or highly active disease (SLEDAI-2K > 8), while Lupus Low Disease Activity State (LLDAS) had inverse associations. Disease activity in other organ domains was not associated with specific gene modules. In contrast, medications were associated with multiple effects. Glucocorticoid use was associated with under-expression of T cell, B cell and plasmablast modules, and over-expression of neutrophil modules. Mycophenolate and azathioprine exposure were associated with plasmablast module and B cell module under-expression respectively. Disease activity associations with neutrophil over-expression and lymphocyte module under-expression were attenuated by multivariable adjustment for medication exposure. CONCLUSION: Medications have significant effect on gene module expression in SLE patients. These findings emphasize the need to control for medications in studies of gene expression in SLE. |
format | Online Article Text |
id | pubmed-9430375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94303752022-09-01 Immunosuppressant exposure confounds gene expression analysis in systemic lupus erythematosus Northcott, Melissa Gearing, Linden J. Bonin, Julie Koelmeyer, Rachel Hoi, Alberta Hertzog, Paul J. Morand, Eric F. Front Immunol Immunology OBJECTIVES: The analysis of gene module expression in SLE is emerging as a tool to identify active biological pathways, with the aim of developing targeted therapies for subsets of patients. Detailed information on the effect of immunosuppressants on gene module expression is lacking. We aimed to examine the impact of medication exposure on gene module expression. METHODS: A set of commercially available disease-relevant gene modules were measured in 730 whole blood samples from a dedicated lupus clinic on whom prospectively collected, contemporaneous clinical data including medication exposure were available. RESULTS: Compared to heathy controls, SLE patients showed over-expression of IFN and under-expression of B cell, T cell and pDC modules. Neutrophil module over-expression and under-expression of B and T cell modules were observed in patients with active lupus nephritis or highly active disease (SLEDAI-2K > 8), while Lupus Low Disease Activity State (LLDAS) had inverse associations. Disease activity in other organ domains was not associated with specific gene modules. In contrast, medications were associated with multiple effects. Glucocorticoid use was associated with under-expression of T cell, B cell and plasmablast modules, and over-expression of neutrophil modules. Mycophenolate and azathioprine exposure were associated with plasmablast module and B cell module under-expression respectively. Disease activity associations with neutrophil over-expression and lymphocyte module under-expression were attenuated by multivariable adjustment for medication exposure. CONCLUSION: Medications have significant effect on gene module expression in SLE patients. These findings emphasize the need to control for medications in studies of gene expression in SLE. Frontiers Media S.A. 2022-08-17 /pmc/articles/PMC9430375/ /pubmed/36059457 http://dx.doi.org/10.3389/fimmu.2022.964263 Text en Copyright © 2022 Northcott, Gearing, Bonin, Koelmeyer, Hoi, Hertzog and Morand https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Northcott, Melissa Gearing, Linden J. Bonin, Julie Koelmeyer, Rachel Hoi, Alberta Hertzog, Paul J. Morand, Eric F. Immunosuppressant exposure confounds gene expression analysis in systemic lupus erythematosus |
title | Immunosuppressant exposure confounds gene expression analysis in systemic lupus erythematosus |
title_full | Immunosuppressant exposure confounds gene expression analysis in systemic lupus erythematosus |
title_fullStr | Immunosuppressant exposure confounds gene expression analysis in systemic lupus erythematosus |
title_full_unstemmed | Immunosuppressant exposure confounds gene expression analysis in systemic lupus erythematosus |
title_short | Immunosuppressant exposure confounds gene expression analysis in systemic lupus erythematosus |
title_sort | immunosuppressant exposure confounds gene expression analysis in systemic lupus erythematosus |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9430375/ https://www.ncbi.nlm.nih.gov/pubmed/36059457 http://dx.doi.org/10.3389/fimmu.2022.964263 |
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