OP0337 DIFFERENTIAL METHYLATION OF PERIPHERAL BLOOD ADAPTIVE IMMUNE CELLS IN INDIVIDUALS AT HIGH RISK FOR RA AND WITH EARLY RA COMPARED WITH CONTROLS IDENTIFIES PATHWAYS IMPORTANT IN TRANSITION TO ARTHRITIS
Background: The “Targeting Immune Responses for Prevention of RA” (TIP-RA) collaboration studies individuals at high risk for developing RA because of serum anti-citrullinated protein antibody positivity in absence of arthritis, and is focused on defining how they transition from at-risk to classifi...
Published in: | Annals of the Rheumatic Diseases |
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crjcrbmj:10.1136/annrheumdis-2020-eular.2989 2024-02-11T10:03:23+01:00 OP0337 DIFFERENTIAL METHYLATION OF PERIPHERAL BLOOD ADAPTIVE IMMUNE CELLS IN INDIVIDUALS AT HIGH RISK FOR RA AND WITH EARLY RA COMPARED WITH CONTROLS IDENTIFIES PATHWAYS IMPORTANT IN TRANSITION TO ARTHRITIS Ai, R. Boyle, D. Hammaker, D. Deane, K. Holers, V. M. Matti, A. Robinson, W. Buckner, J. Rao, N. Baribaud, F. Johnsen, A. Nagpal, S. Wang, W. Firestein, G. 2020 http://dx.doi.org/10.1136/annrheumdis-2020-eular.2989 https://syndication.highwire.org/content/doi/10.1136/annrheumdis-2020-eular.2989 en eng BMJ Annals of the Rheumatic Diseases volume 79, issue Suppl 1, page 207.2-207 ISSN 0003-4967 1468-2060 General Biochemistry, Genetics and Molecular Biology Immunology Immunology and Allergy Rheumatology journal-article 2020 crjcrbmj https://doi.org/10.1136/annrheumdis-2020-eular.2989 2024-01-26T10:16:20Z Background: The “Targeting Immune Responses for Prevention of RA” (TIP-RA) collaboration studies individuals at high risk for developing RA because of serum anti-citrullinated protein antibody positivity in absence of arthritis, and is focused on defining how they transition from at-risk to classifiable disease. One potential mechanism is through alterations in epigenetics patterns in adaptive immune cells. Objectives: Previous studies showed that DNA methylation patterns of early RA (ERA) synoviocytes differ from long-standing RA, suggesting that abnormal methylation occurs early in synovium and evolves over time. To extend these observations, we performed a cross-sectional analysis in TIP-RA of DNA methylation signatures in peripheral blood cells in ERA, at-risk anti-CCP3+ individuals and demographically matched CCP- controls. Methods: Genomic DNA was isolated from two independent cohorts of CCP- (cohorts 1 and 2, respectively: B cell: n = 17/34; memory T cell: n = 21/34; and naïve T cell: n = 21/33), CCP3+ (B cell: n = 18/37; memory T cell: n = 20/36; and naïve T cell: n = 20/35), and CCP3+ ERA (B cell: n = 4/18; memory T cell: n = 5/18; and naïve T cell: n = 5/18) after separating PBMCs using antibodies and magnetic beads. Methylation was measured by Illumina Infinium MethylationEPIC chip. Differentially methylated loci (DMLs) were identified using Welch’s t-test and mapped to gene promoter regions to define DM genes (DMGs). Principal component analysis (PCA) was used to represent relationship among groups. Pathway analysis was applied by Reactome. Results: For the initial cohort, 1494, 1097 and 1330 DMLs were identified among CCP+, CCP- and ERA in B cells, memory T cells and naïve T cells, respectively. For the confirmatory cohort, 523, 793 and 548 DMLs were found in corresponding cell populations. The DML overlap between the 2 cohorts was highly significant ( p = 2.48E-77). The DMLs were combined for both groups and corresponded to 411, 412, and 351 DMGs in B cells, memory T cells and naïve T cells. Of ... Article in Journal/Newspaper DML The BMJ Annals of the Rheumatic Diseases 79 Suppl 1 207.2 207 |
institution |
Open Polar |
collection |
The BMJ |
op_collection_id |
crjcrbmj |
language |
English |
topic |
General Biochemistry, Genetics and Molecular Biology Immunology Immunology and Allergy Rheumatology |
spellingShingle |
General Biochemistry, Genetics and Molecular Biology Immunology Immunology and Allergy Rheumatology Ai, R. Boyle, D. Hammaker, D. Deane, K. Holers, V. M. Matti, A. Robinson, W. Buckner, J. Rao, N. Baribaud, F. Johnsen, A. Nagpal, S. Wang, W. Firestein, G. OP0337 DIFFERENTIAL METHYLATION OF PERIPHERAL BLOOD ADAPTIVE IMMUNE CELLS IN INDIVIDUALS AT HIGH RISK FOR RA AND WITH EARLY RA COMPARED WITH CONTROLS IDENTIFIES PATHWAYS IMPORTANT IN TRANSITION TO ARTHRITIS |
topic_facet |
General Biochemistry, Genetics and Molecular Biology Immunology Immunology and Allergy Rheumatology |
description |
Background: The “Targeting Immune Responses for Prevention of RA” (TIP-RA) collaboration studies individuals at high risk for developing RA because of serum anti-citrullinated protein antibody positivity in absence of arthritis, and is focused on defining how they transition from at-risk to classifiable disease. One potential mechanism is through alterations in epigenetics patterns in adaptive immune cells. Objectives: Previous studies showed that DNA methylation patterns of early RA (ERA) synoviocytes differ from long-standing RA, suggesting that abnormal methylation occurs early in synovium and evolves over time. To extend these observations, we performed a cross-sectional analysis in TIP-RA of DNA methylation signatures in peripheral blood cells in ERA, at-risk anti-CCP3+ individuals and demographically matched CCP- controls. Methods: Genomic DNA was isolated from two independent cohorts of CCP- (cohorts 1 and 2, respectively: B cell: n = 17/34; memory T cell: n = 21/34; and naïve T cell: n = 21/33), CCP3+ (B cell: n = 18/37; memory T cell: n = 20/36; and naïve T cell: n = 20/35), and CCP3+ ERA (B cell: n = 4/18; memory T cell: n = 5/18; and naïve T cell: n = 5/18) after separating PBMCs using antibodies and magnetic beads. Methylation was measured by Illumina Infinium MethylationEPIC chip. Differentially methylated loci (DMLs) were identified using Welch’s t-test and mapped to gene promoter regions to define DM genes (DMGs). Principal component analysis (PCA) was used to represent relationship among groups. Pathway analysis was applied by Reactome. Results: For the initial cohort, 1494, 1097 and 1330 DMLs were identified among CCP+, CCP- and ERA in B cells, memory T cells and naïve T cells, respectively. For the confirmatory cohort, 523, 793 and 548 DMLs were found in corresponding cell populations. The DML overlap between the 2 cohorts was highly significant ( p = 2.48E-77). The DMLs were combined for both groups and corresponded to 411, 412, and 351 DMGs in B cells, memory T cells and naïve T cells. Of ... |
format |
Article in Journal/Newspaper |
author |
Ai, R. Boyle, D. Hammaker, D. Deane, K. Holers, V. M. Matti, A. Robinson, W. Buckner, J. Rao, N. Baribaud, F. Johnsen, A. Nagpal, S. Wang, W. Firestein, G. |
author_facet |
Ai, R. Boyle, D. Hammaker, D. Deane, K. Holers, V. M. Matti, A. Robinson, W. Buckner, J. Rao, N. Baribaud, F. Johnsen, A. Nagpal, S. Wang, W. Firestein, G. |
author_sort |
Ai, R. |
title |
OP0337 DIFFERENTIAL METHYLATION OF PERIPHERAL BLOOD ADAPTIVE IMMUNE CELLS IN INDIVIDUALS AT HIGH RISK FOR RA AND WITH EARLY RA COMPARED WITH CONTROLS IDENTIFIES PATHWAYS IMPORTANT IN TRANSITION TO ARTHRITIS |
title_short |
OP0337 DIFFERENTIAL METHYLATION OF PERIPHERAL BLOOD ADAPTIVE IMMUNE CELLS IN INDIVIDUALS AT HIGH RISK FOR RA AND WITH EARLY RA COMPARED WITH CONTROLS IDENTIFIES PATHWAYS IMPORTANT IN TRANSITION TO ARTHRITIS |
title_full |
OP0337 DIFFERENTIAL METHYLATION OF PERIPHERAL BLOOD ADAPTIVE IMMUNE CELLS IN INDIVIDUALS AT HIGH RISK FOR RA AND WITH EARLY RA COMPARED WITH CONTROLS IDENTIFIES PATHWAYS IMPORTANT IN TRANSITION TO ARTHRITIS |
title_fullStr |
OP0337 DIFFERENTIAL METHYLATION OF PERIPHERAL BLOOD ADAPTIVE IMMUNE CELLS IN INDIVIDUALS AT HIGH RISK FOR RA AND WITH EARLY RA COMPARED WITH CONTROLS IDENTIFIES PATHWAYS IMPORTANT IN TRANSITION TO ARTHRITIS |
title_full_unstemmed |
OP0337 DIFFERENTIAL METHYLATION OF PERIPHERAL BLOOD ADAPTIVE IMMUNE CELLS IN INDIVIDUALS AT HIGH RISK FOR RA AND WITH EARLY RA COMPARED WITH CONTROLS IDENTIFIES PATHWAYS IMPORTANT IN TRANSITION TO ARTHRITIS |
title_sort |
op0337 differential methylation of peripheral blood adaptive immune cells in individuals at high risk for ra and with early ra compared with controls identifies pathways important in transition to arthritis |
publisher |
BMJ |
publishDate |
2020 |
url |
http://dx.doi.org/10.1136/annrheumdis-2020-eular.2989 https://syndication.highwire.org/content/doi/10.1136/annrheumdis-2020-eular.2989 |
genre |
DML |
genre_facet |
DML |
op_source |
Annals of the Rheumatic Diseases volume 79, issue Suppl 1, page 207.2-207 ISSN 0003-4967 1468-2060 |
op_doi |
https://doi.org/10.1136/annrheumdis-2020-eular.2989 |
container_title |
Annals of the Rheumatic Diseases |
container_volume |
79 |
container_issue |
Suppl 1 |
container_start_page |
207.2 |
op_container_end_page |
207 |
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1790599607942643712 |