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Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort
BACKGROUND: Established rheumatoid arthritis (RA) patients display differentially expressed genes coding for cytokine/chemokine-mediated immunity compared to healthy controls. It is unclear, however, if in the pre-arthritis phase of clinically suspect arthralgia (CSA) expression of immune genes diff...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653888/ https://www.ncbi.nlm.nih.gov/pubmed/33168080 http://dx.doi.org/10.1186/s13075-020-02361-2 |
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author | Niemantsverdriet, Ellis van den Akker, Erik B. Boeters, Debbie M. van den Eeden, Susan J. F. Geluk, Annemieke van der Helm-van Mil, Annette H. M. |
author_facet | Niemantsverdriet, Ellis van den Akker, Erik B. Boeters, Debbie M. van den Eeden, Susan J. F. Geluk, Annemieke van der Helm-van Mil, Annette H. M. |
author_sort | Niemantsverdriet, Ellis |
collection | PubMed |
description | BACKGROUND: Established rheumatoid arthritis (RA) patients display differentially expressed genes coding for cytokine/chemokine-mediated immunity compared to healthy controls. It is unclear, however, if in the pre-arthritis phase of clinically suspect arthralgia (CSA) expression of immune genes differ between patients who do or do not develop clinically evident inflammatory arthritis (IA). METHODS: Two hundred thirty-six consecutive patients presenting with arthralgia clinically suspected for progression to RA were followed until IA development or else for median 24 months (IQR 12–26). Baseline whole blood RNA expression was determined for a previously identified set of 133 genes associated with the innate and adaptive immune system by dual-color reverse-transcription multiplex ligation-dependent probe amplification (dcRT-MLPA) profiling. Cox proportional hazard models were used. RESULTS: Twenty percent of CSA patients developed IA. After correction for multiple testing, expression levels of six genes (IFNG, PHEX, IGF-1, IL-7R, CD19, CCR7) at the time of presentation were associated with progression to IA. PHEX and IGF-1 were highly correlated with each other (ρ = 0.97). In multivariable analysis correcting for the different genes, expressions of IL-7R and IGF-1 were independently associated with IA development (p = 0.025, p = 0.046, respectively). Moreover, IL-7R and IGF-1 remained significantly associated even after correction for known predictors (ACPA, CRP, imaging-detected subclinical joint inflammation; p = 0.039, p = 0.005, respectively). These genes are also associated with RA development. CONCLUSIONS: IL-7R and IGF-1 were differentially expressed between CSA patients who did or did not progress to IA, independent from regularly used predictors. These biomarkers may become helpful in prognostication of CSA patients. Furthermore, because both genes are associated with T cell functioning, T cell dysregulation may mediate progression from arthralgia to arthritis. |
format | Online Article Text |
id | pubmed-7653888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-76538882020-11-10 Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort Niemantsverdriet, Ellis van den Akker, Erik B. Boeters, Debbie M. van den Eeden, Susan J. F. Geluk, Annemieke van der Helm-van Mil, Annette H. M. Arthritis Res Ther Research Article BACKGROUND: Established rheumatoid arthritis (RA) patients display differentially expressed genes coding for cytokine/chemokine-mediated immunity compared to healthy controls. It is unclear, however, if in the pre-arthritis phase of clinically suspect arthralgia (CSA) expression of immune genes differ between patients who do or do not develop clinically evident inflammatory arthritis (IA). METHODS: Two hundred thirty-six consecutive patients presenting with arthralgia clinically suspected for progression to RA were followed until IA development or else for median 24 months (IQR 12–26). Baseline whole blood RNA expression was determined for a previously identified set of 133 genes associated with the innate and adaptive immune system by dual-color reverse-transcription multiplex ligation-dependent probe amplification (dcRT-MLPA) profiling. Cox proportional hazard models were used. RESULTS: Twenty percent of CSA patients developed IA. After correction for multiple testing, expression levels of six genes (IFNG, PHEX, IGF-1, IL-7R, CD19, CCR7) at the time of presentation were associated with progression to IA. PHEX and IGF-1 were highly correlated with each other (ρ = 0.97). In multivariable analysis correcting for the different genes, expressions of IL-7R and IGF-1 were independently associated with IA development (p = 0.025, p = 0.046, respectively). Moreover, IL-7R and IGF-1 remained significantly associated even after correction for known predictors (ACPA, CRP, imaging-detected subclinical joint inflammation; p = 0.039, p = 0.005, respectively). These genes are also associated with RA development. CONCLUSIONS: IL-7R and IGF-1 were differentially expressed between CSA patients who did or did not progress to IA, independent from regularly used predictors. These biomarkers may become helpful in prognostication of CSA patients. Furthermore, because both genes are associated with T cell functioning, T cell dysregulation may mediate progression from arthralgia to arthritis. BioMed Central 2020-11-09 2020 /pmc/articles/PMC7653888/ /pubmed/33168080 http://dx.doi.org/10.1186/s13075-020-02361-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Niemantsverdriet, Ellis van den Akker, Erik B. Boeters, Debbie M. van den Eeden, Susan J. F. Geluk, Annemieke van der Helm-van Mil, Annette H. M. Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort |
title | Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort |
title_full | Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort |
title_fullStr | Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort |
title_full_unstemmed | Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort |
title_short | Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort |
title_sort | gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653888/ https://www.ncbi.nlm.nih.gov/pubmed/33168080 http://dx.doi.org/10.1186/s13075-020-02361-2 |
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