Activated Peripheral Blood B Cells in Rheumatoid Arthritis and Their Relationship to Anti-Tumor Necrosis Factor Treatment and Response: A Randomized Clinical Trial of the Effects of Anti-Tumor Necrosis Factor on B Cells.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
11
06
2021
received:
18
11
2020
accepted:
29
07
2021
pubmed:
5
8
2021
medline:
19
2
2022
entrez:
4
8
2021
Statut:
ppublish
Résumé
B cells can become activated in germinal center (GC) reactions in secondary lymphoid tissue and in ectopic GCs in rheumatoid arthritis (RA) synovium that may be tumor necrosis factor (TNF) and lymphotoxin (LT) dependent. This study was undertaken to characterize the peripheral B cell compartment longitudinally during anti-TNF therapy in RA. Participants were randomized in a 2:1 ratio to receive standard dosing regimens of etanercept (n = 43) or adalimumab (n = 20) for 24 weeks. Eligible participants met the American College of Rheumatology 1987 criteria for RA, had clinically active disease (Disease Activity Score in 28 joints >4.4), and were receiving stable doses of methotrexate. The primary mechanistic end point was the change in switched memory B cell fraction from baseline to week 12 in each treatment group. B cell subsets remained surprisingly stable over the course of the study regardless of treatment group, with no significant change in memory B cells. Blockade of TNF and LT with etanercept compared to blockade of TNF alone with adalimumab did not translate into significant differences in clinical response. The frequencies of multiple activated B cell populations, including CD21- double-negative memory and activated naive B cells, were higher in RA nonresponders at all time points, and CD95+ activated B cell frequencies were increased in patients receiving anti-TNF treatment in the nonresponder group. In contrast, frequencies of transitional B cells-a putative regulatory subset-were lower in the nonresponders. Overall, our results support the notion that peripheral blood B cell subsets are remarkably stable in RA and not differentially impacted by dual blockade of TNF and LT with etanercept or single blockade of TNF with adalimumab. Activated B cells do associate with a less robust response.
Identifiants
pubmed: 34347945
doi: 10.1002/art.41941
pmc: PMC8795463
mid: NIHMS1729405
doi:
Substances chimiques
Antirheumatic Agents
0
Tumor Necrosis Factor Inhibitors
0
Adalimumab
FYS6T7F842
Etanercept
OP401G7OJC
Banques de données
ClinicalTrials.gov
['NCT00837434']
Types de publication
Clinical Trial, Phase IV
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
200-211Subventions
Organisme : NIAID NIH HHS
ID : UM2 AI117870
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI056390
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI077674
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : U19 AI563262
Organisme : NIAID NIH HHS
ID : P01 AI078907
Pays : United States
Informations de copyright
© 2021, American College of Rheumatology.
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