Evidence map›Paper›PMID 36716083›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2023

Identification of Cell-Specific Differential DNA Methylation Associated With Methotrexate Treatment Response in Rheumatoid Arthritis.

Cameron Adams, Nisha Nair, Darren Plant, Suzanne M M Verstappen, Hong L Quach, Diana L Quach, Alex Carvidi, Joanne Nititham, Mary Nakamura, Jonathan Graf and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% of its field
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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. International journal of molecular medicine · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Epigenomics · 2025
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. An ElevatedCurrent issues in molecular biology · 2024
    Article
  17. Role of IFN-α in Rheumatoid Arthritis.Current rheumatology reports · 2024
    Review
  18. Article
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

13 authors at 7 institutions in 2 countries.

Cameron AdamsSchool of Public Health, University of California, Berkeley.ORCID 0000-0003-2525-523X
Nisha NairCentre of Genetics and Genomics Versus Arthritis, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK.
Darren PlantCentre of Genetics and Genomics Versus Arthritis, Manchester Academic Health Sciences Centre, NIHR Manchester BRC, Manchester University Foundation Trust, The University of Manchester, Manchester, UK.
Suzanne M M VerstappenNIHR Manchester BRC, Manchester University Foundation Trust, and Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and Dermatological Sciences, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK, Institute of Cellular Medicine, Newcastle University, and NIHR Newcastle BRC, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Hong L QuachSchool of Public Health, University of California, Berkeley.
Diana L QuachSchool of Public Health, University of California, Berkeley.
Alex CarvidiUniversity of California, San Francisco.
Joanne NitithamNational Human Genome Research Institute, NIH, Bethesda, Maryland.
Mary NakamuraUniversity of California and San Francisco Veterans Administration Health System, San Francisco, California.
Jonathan GrafUniversity of California, San Francisco.
Anne BartonCentre of Genetics and Genomics Versus Arthritis, Manchester Academic Health Sciences Centre, NIHR Manchester BRC, Manchester University Foundation Trust, The University of Manchester, Manchester, UK.
Lindsey A CriswellNational Human Genome Research Institute, NIH, Bethesda, Maryland.
Lisa F BarcellosSchool of Public Health, University of California, Berkeley, and National Human Genome Research Institute, NIH, Bethesda, Maryland.ORCID 0000-0002-0303-3479
Berkeley Public Health Division · USNational Human Genome Research Institute · USUniversity of California, San Francisco · USUniversity of Manchester · GBManchester Academic Health Science Centre · GBNewcastle upon Tyne Hospitals NHS Foundation Trust · GBSan Francisco VA Health Care System · US

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
Genomic studies of Systemic Lupus ErythematosusZIAHG200416 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI CRISWELL, LINDSEY · 2021 to 2025
$7.0M
Establishing the Role of Genetic Variation in Vitamin D Regulated Gene Expression in MS Pathogenesis and SeverityF31NS113537 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI ADAMS, CAMERON · 2020 to 2022
$109k
NIAMS NIH HHS P30 AR070155NINDS NIH HHS 1F31NS113537-01A1NINDS NIH HHS F31 NS113537
6 · The paper itself

Abstract

objectiveWe undertook this study to estimate changes in cell-specific DNA methylation (DNAm) associated with methotrexate (MTX) response using whole blood samples collected from rheumatoid arthritis (RA) patients before and after initiation of MTX treatment.

methodsPatients included in this study were from the Rheumatoid Arthritis Medication Study (n = 66) and the University of California San Francisco Rheumatoid Arthritis study (n = 11). All patients met the American College of Rheumatology RA classification criteria. Blood samples were collected at baseline and following treatment. Disease Activity Scores in 28 joints using the C-reactive protein level were collected at baseline and after 3-6 months of treatment with MTX. Methylation profiles were generated using the Illumina Infinium HumanMethylation450 and MethylationEPIC v1.0 BeadChip arrays using DNA from whole blood. MTX response was defined using the EULAR response criteria (responders showed good/moderate response; nonresponders showed no response). Differentially methylated positions were identified using the Limma software package and Tensor Composition Analysis, which is a method for identifying cell-specific differential DNAm at the CpG level from tissue-level ("bulk") data. Differentially methylated regions were identified using Comb-p software.

resultsWe found evidence of differential global methylation between treatment response groups. Further, we found patterns of cell-specific differential global methylation associated with MTX response. After correction for multiple testing, 1 differentially methylated position was associated with differential DNAm between responders and nonresponders at baseline in CD4+ T cells, CD8+ T cells, and natural killer cells. Thirty-nine cell-specific differentially methylated regions associated with MTX treatment response were identified. There were no significant findings in analyses of whole blood samples.

conclusionWe identified cell-specific changes in DNAm that were associated with MTX treatment response in RA patients. Future studies of DNAm and MTX treatment response should include measurements of DNAm from sorted cells.

Indexed as

Antirheumatic AgentsArthritis, RheumatoidDNADNA MethylationHumansMethotrexateTreatment OutcomeAntirheumatic AgentsDNAMethotrexate

Identifiers

PMID36716083
PMCPMC10313739
OpenAlexW4318484521

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.