Serum miRNA Signature in Rheumatoid Arthritis and “At-Risk Individuals”
BackgroundMicroRNAs (miRNAs) are small non-coding RNAs which have been implicated as potential biomarkers or therapeutic targets in autoimmune diseases. This study examines circulatory miRNAs in RA patients and further investigates if a serum miRNA signature precedes clinical manifestations of disea...
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Frontiers Media S.A.
2021-03-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.633201/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Clare C. Cunningham Clare C. Cunningham Sarah Wade Sarah Wade Achilleas Floudas Achilleas Floudas Carl Orr Trudy McGarry Trudy McGarry Siobhan Wade Siobhan Wade Sian Cregan Ursula Fearon Ursula Fearon Douglas J. Veale |
spellingShingle |
Clare C. Cunningham Clare C. Cunningham Sarah Wade Sarah Wade Achilleas Floudas Achilleas Floudas Carl Orr Trudy McGarry Trudy McGarry Siobhan Wade Siobhan Wade Sian Cregan Ursula Fearon Ursula Fearon Douglas J. Veale Serum miRNA Signature in Rheumatoid Arthritis and “At-Risk Individuals” Frontiers in Immunology rheumatoid arthritis microRNA inflammation arthralgia therapy at-risk individuals |
author_facet |
Clare C. Cunningham Clare C. Cunningham Sarah Wade Sarah Wade Achilleas Floudas Achilleas Floudas Carl Orr Trudy McGarry Trudy McGarry Siobhan Wade Siobhan Wade Sian Cregan Ursula Fearon Ursula Fearon Douglas J. Veale |
author_sort |
Clare C. Cunningham |
title |
Serum miRNA Signature in Rheumatoid Arthritis and “At-Risk Individuals” |
title_short |
Serum miRNA Signature in Rheumatoid Arthritis and “At-Risk Individuals” |
title_full |
Serum miRNA Signature in Rheumatoid Arthritis and “At-Risk Individuals” |
title_fullStr |
Serum miRNA Signature in Rheumatoid Arthritis and “At-Risk Individuals” |
title_full_unstemmed |
Serum miRNA Signature in Rheumatoid Arthritis and “At-Risk Individuals” |
title_sort |
serum mirna signature in rheumatoid arthritis and “at-risk individuals” |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-03-01 |
description |
BackgroundMicroRNAs (miRNAs) are small non-coding RNAs which have been implicated as potential biomarkers or therapeutic targets in autoimmune diseases. This study examines circulatory miRNAs in RA patients and further investigates if a serum miRNA signature precedes clinical manifestations of disease in arthralgia or “at-risk individuals”.MethodsSerum was collected from HC subjects (N = 20), RA patients (N = 50), and arthralgia subjects (N = 10), in addition to a subgroup of the RA patients post-methotrexate (MTX) (N = 18). The FirePlex miRNA Immunology-V2 panel was selected for multiplex analysis of 68 miRNAs in each sample. DNA intelligent analysis (DIANA)-mirPath and Ingenuity Pathway Analysis (IPA) software were used to predict pathways targeted by the dysregulated miRNAs.Results8 miRNA (miR-126-3p, let-7d-5p, miR-431-3p, miR-221-3p, miR-24-3p, miR-130a-3p, miR-339-5p, let-7i-5p) were significantly elevated in RA serum compared to HC (all p < 0.01) and 1 miRNA (miR-17-5p) was significantly lower in RA (p < 0.01). High specificity and sensitivity were determined by receiver operating characteristic (ROC) curve analysis. Both miR-339-5p and let-7i-5p were significantly reduced post-MTX (both p < 0.01). MiR-126-3p, let-7d-5p, miR-431-3p, miR-221-3p, miR-24-3p, miR-130a-3p were also significantly elevated in subjects “at risk” of developing RA (all p < 0.05) compared to HC. IPA analysis of this miRNA signature identified downstream targets including key transcription factors NF-κB, STAT-1, STAT-3, cytokines IL-1β, TNF-α, and matrix-metalloproteases all importantly associated with RA pathogenesis.ConclusionThis study identified six miRNAs that are altered in both RA and “at-risk individuals,” which potentially regulate key downstream pathways involved in regulating inflammation. These may have potential as predictive signature for disease onset and early progression. |
topic |
rheumatoid arthritis microRNA inflammation arthralgia therapy at-risk individuals |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.633201/full |
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doaj-97005a631c7646aa88935067eb0b04a62021-03-03T05:59:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.633201633201Serum miRNA Signature in Rheumatoid Arthritis and “At-Risk Individuals”Clare C. Cunningham0Clare C. Cunningham1Sarah Wade2Sarah Wade3Achilleas Floudas4Achilleas Floudas5Carl Orr6Trudy McGarry7Trudy McGarry8Siobhan Wade9Siobhan Wade10Sian Cregan11Ursula Fearon12Ursula Fearon13Douglas J. Veale14Molecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, IrelandEUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, IrelandMolecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, IrelandEUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, IrelandMolecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, IrelandEUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, IrelandEUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, IrelandMolecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, IrelandEUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, IrelandMolecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, IrelandEUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, IrelandEUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, IrelandMolecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, IrelandEUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, IrelandEUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, IrelandBackgroundMicroRNAs (miRNAs) are small non-coding RNAs which have been implicated as potential biomarkers or therapeutic targets in autoimmune diseases. This study examines circulatory miRNAs in RA patients and further investigates if a serum miRNA signature precedes clinical manifestations of disease in arthralgia or “at-risk individuals”.MethodsSerum was collected from HC subjects (N = 20), RA patients (N = 50), and arthralgia subjects (N = 10), in addition to a subgroup of the RA patients post-methotrexate (MTX) (N = 18). The FirePlex miRNA Immunology-V2 panel was selected for multiplex analysis of 68 miRNAs in each sample. DNA intelligent analysis (DIANA)-mirPath and Ingenuity Pathway Analysis (IPA) software were used to predict pathways targeted by the dysregulated miRNAs.Results8 miRNA (miR-126-3p, let-7d-5p, miR-431-3p, miR-221-3p, miR-24-3p, miR-130a-3p, miR-339-5p, let-7i-5p) were significantly elevated in RA serum compared to HC (all p < 0.01) and 1 miRNA (miR-17-5p) was significantly lower in RA (p < 0.01). High specificity and sensitivity were determined by receiver operating characteristic (ROC) curve analysis. Both miR-339-5p and let-7i-5p were significantly reduced post-MTX (both p < 0.01). MiR-126-3p, let-7d-5p, miR-431-3p, miR-221-3p, miR-24-3p, miR-130a-3p were also significantly elevated in subjects “at risk” of developing RA (all p < 0.05) compared to HC. IPA analysis of this miRNA signature identified downstream targets including key transcription factors NF-κB, STAT-1, STAT-3, cytokines IL-1β, TNF-α, and matrix-metalloproteases all importantly associated with RA pathogenesis.ConclusionThis study identified six miRNAs that are altered in both RA and “at-risk individuals,” which potentially regulate key downstream pathways involved in regulating inflammation. These may have potential as predictive signature for disease onset and early progression.https://www.frontiersin.org/articles/10.3389/fimmu.2021.633201/fullrheumatoid arthritismicroRNAinflammationarthralgiatherapyat-risk individuals |