Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients.
Adult
Aged
Antirheumatic Agents
/ therapeutic use
Arthritis, Rheumatoid
/ diagnostic imaging
Biomarkers
/ blood
Biopsy
Disease Progression
Female
Gene Expression Regulation
Humans
Longitudinal Studies
Male
Middle Aged
Phenotype
Prognosis
Radiography
Severity of Illness Index
Synovial Membrane
/ metabolism
Transcriptome
Ultrasonography, Interventional
/ methods
dmards (synthetic)
early rheumatoid arthritis
inflammation
synovitis
Journal
Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
06
10
2018
revised:
06
02
2019
accepted:
14
02
2019
pubmed:
18
3
2019
medline:
30
1
2020
entrez:
18
3
2019
Statut:
ppublish
Résumé
To unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally. 144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. Differential gene expression analysis and logistic regression were applied to define variables correlating with treatment response and predicting radiographic progression. Cellular and molecular analyses of synovial tissue demonstrated for the first time in early RA the presence of three pathology groups: (1) We demonstrate at disease presentation, prior to pathology modulation by therapy, the presence of specific cellular/molecular synovial signatures that delineate disease severity/progression and therapeutic response and may pave the way to more precise definition of RA taxonomy, therapeutic targeting and improved outcomes.
Identifiants
pubmed: 30878974
pii: annrheumdis-2018-214539
doi: 10.1136/annrheumdis-2018-214539
pmc: PMC6579551
doi:
Substances chimiques
Antirheumatic Agents
0
Biomarkers
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
761-772Subventions
Organisme : Medical Research Council
ID : G0800648
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K015346/1
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : 20670
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
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