Evidence map›Paper›PMID 39696438›Full record

ArticleClinical epigenetics2024

Changes in DNA methylation are associated with systemic lupus erythematosus flare remission and clinical subtypes.

Mary K Horton, Joanne Nititham, Kimberly E Taylor, Patricia Katz, Chun Jimmie Ye, Jinoos Yazdany, Maria Dall'Era, Charlotte Hurabielle, Lisa F Barcellos, Lindsey A Criswell and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Mary K HortonGenomics of Autoimmune Rheumatic Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. mary.horton@nih.gov.
Joanne NitithamGenomics of Autoimmune Rheumatic Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Kimberly E TaylorDivision of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Patricia KatzDivision of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Chun Jimmie YeBakar Computational Health Sciences Institute, University of California, San Francisco, CA, USA.
Jinoos YazdanyDivision of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Maria Dall'EraDivision of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Charlotte HurabielleDivision of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Lisa F BarcellosDivision of Epidemiology, University of California, Berkeley, CA, USA.
Lindsey A CriswellGenomics of Autoimmune Rheumatic Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Cristina M LanataGenomics of Autoimmune Rheumatic Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

Funding

RESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2M
Racial/ethnic and socioeconomic disparities in biologic and clinical SLE outcomesU01DP006701 · DP · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DALL'ERA, MARIA, YAZDANY, JINOOS · 2022 to 2025
$3.6M
Academic Rheumatology and Clinical ImmunologyT32AR079068 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jinoos Yazdany, JULIE ZIKHERMAN · 2021 to 2026
$2.5M
CDC HHS U01DP006701NCCDPHP CDC HHS U01 DP006701NIAMS NIH HHS P30 AR070155NIAMS NIH HHS T32 AR079068
6 · The paper itself

Abstract

backgroundSystemic lupus erythematosus (SLE) has numerous symptoms across organs and an unpredictable flare-remittance pattern. This has made it challenging to understand drivers of long-term SLE outcomes. Our objective was to identify whether changes in DNA methylation over time, in an actively flaring SLE cohort, were associated with remission and whether these changes meaningfully subtype SLE patients.

methodsFifty-nine multi-ethnic SLE patients had clinical visits and DNA methylation profiles at a flare and approximately 3 months later. Methylation was measured using the Illumina EPIC array. We identified sites where methylation change between visits was associated with remission at the follow-up visit using limma package and a time x remission interaction term. Models adjusted for batch, age at diagnosis, time between visits, age at flare, sex, medications, and cell-type proportions. Separately, a paired T-test identified Bonferroni significant methylation sites with ≥ 3% change between visits (n = 546). Methylation changes at these sites were used for unsupervised consensus hierarchical clustering. Associations between clusters and patient features were assessed.

resultsNineteen patients fully remitted at the follow-up visit. For 1,953 CpG sites, methylation changed differently for remitters vs. non-remitters (Bonferroni p < 0.05). Nearly half were within genes regulated by interferon. The largest effect was at cg22873177; on average, remitters had 23% decreased methylation between visits while non-remitters had no change. Three SLE patient clusters were identified using methylation differences agnostic of clinical outcomes. All Cluster 1 subjects (n = 12) experienced complete flare remission, despite similar baseline disease activity scores, medications, and demographics as other clusters. Methylation changes at six CpG sites, including within immune-related CD45 and IFI genes, were particularly distinct for each cluster, suggesting these may be good candidates for stratifying patients in the future.

conclusionsChanges in DNA methylation during active SLE were associated with remission status and identified subgroups of SLE patients with several distinct clinical and biological characteristics. DNA methylation patterns might help inform SLE subtypes, leading to targeted therapies based on relevant underlying biological pathways.

Indexed as

DNA MethylationLupus Erythematosus, SystemicAdultCpG IslandsEpigenesis, GeneticFemaleHumansMaleMiddle AgedRemission InductionDisease subtypingDNA methylationHierarchical clusteringLongitudinalLupus flareLupus remissionSystemic lupus erythematosusUnsupervised machine learning

Identifiers

PMID39696438
PMCPMC11656870

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.