Evidence map›Paper›PMID 38954480›Full record

ArticleJCI insight2024

Single-cell RNA-Seq analysis reveals cell subsets and gene signatures associated with rheumatoid arthritis disease activity.

Marie Binvignat, Brenda Y Miao, Camilla Wibrand, Monica M Yang, Dmitry Rychkov, Emily Flynn, Joanne Nititham, Whitney Tamaki, Umair Khan, Alexander Carvidi and 13 more

Abstract read
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
–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

36 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  10. Medea: An omics AI agent for therapeutic discovery.bioRxiv : the preprint server for biology · 2026
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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

23 authors.

Marie BinvignatBakar Computational Health Sciences Institute, UCSF, San Francisco, California, USA.
Brenda Y MiaoBakar Computational Health Sciences Institute, UCSF, San Francisco, California, USA.
Camilla WibrandBakar Computational Health Sciences Institute, UCSF, San Francisco, California, USA.
Monica M YangRosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Division of Rheumatology, Department of Medicine, and.
Dmitry RychkovBakar Computational Health Sciences Institute, UCSF, San Francisco, California, USA.
Emily FlynnRosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Division of Rheumatology, Department of Medicine, and.
Joanne NitithamRosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Division of Rheumatology, Department of Medicine, and.
Whitney TamakiBakar Computational Health Sciences Institute, UCSF, San Francisco, California, USA.
Umair KhanBakar Computational Health Sciences Institute, UCSF, San Francisco, California, USA.
Alexander CarvidiRosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Division of Rheumatology, Department of Medicine, and.
Melissa KruegerDepartment of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Erene NiemiRosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Division of Rheumatology, Department of Medicine, and.
Yang SunDepartment of Human Genetics and.
Gabriela K FragiadakisRosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Division of Rheumatology, Department of Medicine, and.
Jérémie SellamDepartment of Rheumatology, Research Center Saint Antoine, UMRS 938, Sorbonne University, AP-HP, Saint-Antoine Hospital, Inserm UMRS 938, Paris, France.
Encarnita Mariotti-FerrandizImmunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne University, Paris, France.
David KlatzmannImmunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne University, Paris, France.
Andrew J GrossRosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Division of Rheumatology, Department of Medicine, and.
Chun Jimmie YeDepartment of Human Genetics and.
Atul J ButteBakar Computational Health Sciences Institute, UCSF, San Francisco, California, USA.
Lindsey A CriswellRosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Division of Rheumatology, Department of Medicine, and.
Mary C NakamuraRosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Division of Rheumatology, Department of Medicine, and.
Marina SirotaBakar Computational Health Sciences Institute, UCSF, San Francisco, California, 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
Skeletal Biology and Biomechanics (SBB) CoreP30AR075055 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EDWARD C HSIAO · 2019 to 2026
$7.1M
NIAMS NIH HHS P30 AR070155NIAMS NIH HHS P30 AR075055
6 · The paper itself

Abstract

Rheumatoid arthritis (RA) management leans toward achieving remission or low disease activity. In this study, we conducted single-cell RNA sequencing (scRNA-Seq) of peripheral blood mononuclear cells (PBMCs) from 36 individuals (18 patients with RA and 18 matched controls, accounting for age, sex, race, and ethnicity), to identify disease-relevant cell subsets and cell type-specific signatures associated with disease activity. Our analysis revealed 18 distinct PBMC subsets, including an IFN-induced transmembrane 3-overexpressing (IFITM3-overexpressing) IFN-activated monocyte subset. We observed an increase in CD4+ T effector memory cells in patients with moderate-high disease activity (DAS28-CRP ≥ 3.2) and a decrease in nonclassical monocytes in patients with low disease activity or remission (DAS28-CRP < 3.2). Pseudobulk analysis by cell type identified 168 differentially expressed genes between RA and matched controls, with a downregulation of proinflammatory genes in the γδ T cell subset, alteration of genes associated with RA predisposition in the IFN-activated subset, and nonclassical monocytes. Additionally, we identified a gene signature associated with moderate-high disease activity, characterized by upregulation of proinflammatory genes such as TNF, JUN, EGR1, IFIT2, MAFB, and G0S2 and downregulation of genes including HLA-DQB1, HLA-DRB5, and TNFSF13B. Notably, cell-cell communication analysis revealed an upregulation of signaling pathways, including VISTA, in both moderate-high and remission-low disease activity contexts. Our findings provide valuable insights into the systemic cellular and molecular mechanisms underlying RA disease activity.

Indexed as

Arthritis, RheumatoidRNA-SeqSingle-Cell Gene Expression AnalysisAdultAgedCase-Control StudiesFemaleHumansLeukocytes, MononuclearMaleMiddle AgedMonocytesTranscriptomeAutoimmunityImmunologyRheumatology

Identifiers

PMID38954480
PMCPMC11343607

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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.