Associations Between Rheumatoid Arthritis Clinical Factors and Synovial Cell Types and States.

Autor: Weisenfeld D; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Zhang F; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.; University of Colorado School of Medicine, Aurora, Colorado., Donlin L; Weill Cornell Medicine and Hospital for Special Surgery, New York, New York., Jonsson AH; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Apruzzese W; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Accelerated Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus Network., Campbell D; University of Rochester Medical Center, Rochester, New York., Rao DA; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Wei K; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Holers VM; University of Colorado School of Medicine, Aurora, Colorado., Gravallese E; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Moreland L; University of Colorado School of Medicine, Aurora, Colorado.; University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania., Goodman S; Weill Cornell Medicine and Hospital for Special Surgery, New York, New York., Brenner M; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Raychaudhuri S; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Filer A; NIHR Birmingham Biomedical Research Center and Clinical Research Facility, Versus Arthritis, and University of Birmingham, Birmingham, UK., Anolik J; University of Rochester Medical Center, Rochester, New York., Bykerk V; Weill Cornell Medicine and Hospital for Special Surgery, New York, New York., Liao KP; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2024 Mar; Vol. 76 (3), pp. 356-362. Date of Electronic Publication: 2024 Jan 19.
DOI: 10.1002/art.42726
Abstrakt: Objective: Recent studies have uncovered diverse cell types and states in the rheumatoid arthritis (RA) synovium; however, limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multicell data, we determined associations between RA clinical factors with cell types and states in the RA synovium.
Methods: The Accelerated Medicines Partnership Rheumatoid Arthritis study recruited patients with active RA who were not receiving disease-modifying antirheumatic drugs (DMARDs) or who had an inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint, and tissue were disaggregated and processed with a cellular indexing of transcriptomes and epitopes sequencing pipeline from which the following cell type percentages and cell type abundance phenotypes (CTAPs) were derived: endothelial, fibroblast, and myeloid (EFM); fibroblasts; myeloid; T and B cells; T cells and fibroblasts (TF); and T and myeloid cells. Correlations were measured between RA clinical factors, cell type percentage, and CTAPs.
Results: We studied 72 patients (mean age 57 years, 75% women, 83% seropositive, mean RA duration 6.6 years, mean Disease Activity Score-28 C-reactive Protein 3 [DAS28-CRP3] score 4.8). Higher DAS28-CRP3 correlated with a higher T cell percentage (P < 0.01). Those receiving MTX and not a biologic DMARD (bDMARD) had a higher percentage of B cells versus those receiving no DMARDs (P < 0.01). Most of those receiving bDMARDs were categorized as EFM (57%), whereas none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, or DAS28-CRP3.
Conclusion: In this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors, may impact cell type/state in the synovium and ultimately influence response to subsequent therapies.
(© 2023 American College of Rheumatology.)
Databáze: MEDLINE
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