Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis
Background: Antibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses. Methods: A case...
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Umeå universitet, Reumatologi
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ftumeauniv:oai:DiVA.org:umu-168174 2023-10-09T21:54:36+02:00 Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis Brink, Mikael Lundquist, Anders Alexeyenko, Andrey Lejon, Kristina Rantapää-Dahlqvist, Solbritt 2019 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-168174 https://doi.org/10.1186/s13075-019-2066-9 eng eng Umeå universitet, Reumatologi Umeå universitet, Immunologi/immunkemi Arthritis Research & Therapy, 1478-6354, 2019, 21:1, orcid:0000-0001-7675-3488 orcid:0000-0003-1524-0851 orcid:0000-0001-5025-6539 orcid:0000-0001-8259-3863 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-168174 doi:10.1186/s13075-019-2066-9 PMID 31842970 ISI:000509121200002 Scopus 2-s2.0-85076694539 info:eu-repo/semantics/openAccess Rheumatoid arthritis Pre-symptomatic stage Protein levels Plasma biomarkers Rheumatology and Autoimmunity Reumatologi och inflammation Article in journal info:eu-repo/semantics/article text 2019 ftumeauniv https://doi.org/10.1186/s13075-019-2066-9 2023-09-22T13:58:18Z Background: Antibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses. Methods: A case-control study was conducted within the Biobank of northern Sweden. The plasma samples from 118 pre-symptomatic individuals (207 samples; median predating time 4.1 years), 79 early RA patients, and 74 matched controls were analyzed. The levels of 122 unique proteins with an acknowledged relationship to autoimmunity were analyzed using 153 antibodies and a bead-based multiplex system (FlexMap3D; Luminex Corp.). The data were analyzed using multifactorial linear regression model, random forest, and network enrichment analysis (NEA) based on the 10 most significantly differentially expressed proteins for each two-by-two group comparison, using the MSigDB collection of hallmarks. Results: There was a high agreement between the different statistical methods to identify the most significant proteins. The adipogenesis and interferon alpha response hallmarks differentiated pre-symptomatic individuals from controls. These two hallmarks included proteins involved in innate immunity. Between pre-symptomatic individuals and RA patients, three hallmarks were identified as follows: apical junction, epithelial mesenchymal transition, and TGF-beta signaling, including proteins suggestive of cell interaction, remodulation, and fibrosis. The adipogenesis and heme metabolism hallmarks differentiated RA patients from controls. Conclusions: We confirm the importance of interferon alpha signaling and lipids in the early phases of RA development. Network enrichment analysis provides a tool for a deeper understanding of molecules involved at different phases of the disease progression. Article in Journal/Newspaper Northern Sweden Umeå University: Publications (DiVA) Arthritis Research & Therapy 21 1 |
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Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
Rheumatoid arthritis Pre-symptomatic stage Protein levels Plasma biomarkers Rheumatology and Autoimmunity Reumatologi och inflammation |
spellingShingle |
Rheumatoid arthritis Pre-symptomatic stage Protein levels Plasma biomarkers Rheumatology and Autoimmunity Reumatologi och inflammation Brink, Mikael Lundquist, Anders Alexeyenko, Andrey Lejon, Kristina Rantapää-Dahlqvist, Solbritt Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
topic_facet |
Rheumatoid arthritis Pre-symptomatic stage Protein levels Plasma biomarkers Rheumatology and Autoimmunity Reumatologi och inflammation |
description |
Background: Antibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses. Methods: A case-control study was conducted within the Biobank of northern Sweden. The plasma samples from 118 pre-symptomatic individuals (207 samples; median predating time 4.1 years), 79 early RA patients, and 74 matched controls were analyzed. The levels of 122 unique proteins with an acknowledged relationship to autoimmunity were analyzed using 153 antibodies and a bead-based multiplex system (FlexMap3D; Luminex Corp.). The data were analyzed using multifactorial linear regression model, random forest, and network enrichment analysis (NEA) based on the 10 most significantly differentially expressed proteins for each two-by-two group comparison, using the MSigDB collection of hallmarks. Results: There was a high agreement between the different statistical methods to identify the most significant proteins. The adipogenesis and interferon alpha response hallmarks differentiated pre-symptomatic individuals from controls. These two hallmarks included proteins involved in innate immunity. Between pre-symptomatic individuals and RA patients, three hallmarks were identified as follows: apical junction, epithelial mesenchymal transition, and TGF-beta signaling, including proteins suggestive of cell interaction, remodulation, and fibrosis. The adipogenesis and heme metabolism hallmarks differentiated RA patients from controls. Conclusions: We confirm the importance of interferon alpha signaling and lipids in the early phases of RA development. Network enrichment analysis provides a tool for a deeper understanding of molecules involved at different phases of the disease progression. |
format |
Article in Journal/Newspaper |
author |
Brink, Mikael Lundquist, Anders Alexeyenko, Andrey Lejon, Kristina Rantapää-Dahlqvist, Solbritt |
author_facet |
Brink, Mikael Lundquist, Anders Alexeyenko, Andrey Lejon, Kristina Rantapää-Dahlqvist, Solbritt |
author_sort |
Brink, Mikael |
title |
Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
title_short |
Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
title_full |
Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
title_fullStr |
Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
title_full_unstemmed |
Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
title_sort |
protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
publisher |
Umeå universitet, Reumatologi |
publishDate |
2019 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-168174 https://doi.org/10.1186/s13075-019-2066-9 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Arthritis Research & Therapy, 1478-6354, 2019, 21:1, orcid:0000-0001-7675-3488 orcid:0000-0003-1524-0851 orcid:0000-0001-5025-6539 orcid:0000-0001-8259-3863 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-168174 doi:10.1186/s13075-019-2066-9 PMID 31842970 ISI:000509121200002 Scopus 2-s2.0-85076694539 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1186/s13075-019-2066-9 |
container_title |
Arthritis Research & Therapy |
container_volume |
21 |
container_issue |
1 |
_version_ |
1779318236909666304 |