JAK inhibitors differentially modulate B cell activation, maturation and function: A comparative analysis of five JAK inhibitors in an
B cells
JAK inhibition
baricitinib
filgotinib
rheumatoid arthritis
ruxolitinib
tofacitinib
upadacitinib
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
02
11
2022
accepted:
09
01
2023
entrez:
13
2
2023
pubmed:
14
2
2023
medline:
15
2
2023
Statut:
epublish
Résumé
Janus kinase (JAK) inhibitors have been approved for the treatment of several immune-mediated diseases (IMIDs) including rheumatoid arthritis (RA) and psoriatic arthritis and are in clinical trials for numerous other IMIDs. However, detailed studies investigating the effects of different JAK inhibitors on B cells are missing. Within this study, we therefore aimed to characterize the effect of JAK inhibition on the B cell compartment. To this end, we investigated the B cell compartment under JAK inhibition and compared the specific effects of the different JAK inhibitors tofacitinib (pan-JAK), baricitinib (JAK1/2), ruxolitinib (JAK1/2), upadacitinib (JAK1/2) as well as filgotinib (selective JAK1) on While B cell phenotyping of RA patients showed an increase in marginal zone (MZ) B cells under JAK inhibition, comparison with healthy donors revealed that the relative frequency of MZ B cells was still lower compared to healthy controls. In an JAK inhibition has a major effect on B cell activation and differentiation, with differential outcomes between JAK inhibitors hinting towards distinct and unique effects on B cell homeostasis.
Sections du résumé
Background
Janus kinase (JAK) inhibitors have been approved for the treatment of several immune-mediated diseases (IMIDs) including rheumatoid arthritis (RA) and psoriatic arthritis and are in clinical trials for numerous other IMIDs. However, detailed studies investigating the effects of different JAK inhibitors on B cells are missing. Within this study, we therefore aimed to characterize the effect of JAK inhibition on the B cell compartment.
Methods
To this end, we investigated the B cell compartment under JAK inhibition and compared the specific effects of the different JAK inhibitors tofacitinib (pan-JAK), baricitinib (JAK1/2), ruxolitinib (JAK1/2), upadacitinib (JAK1/2) as well as filgotinib (selective JAK1) on
Results
While B cell phenotyping of RA patients showed an increase in marginal zone (MZ) B cells under JAK inhibition, comparison with healthy donors revealed that the relative frequency of MZ B cells was still lower compared to healthy controls. In an
Conclusion
JAK inhibition has a major effect on B cell activation and differentiation, with differential outcomes between JAK inhibitors hinting towards distinct and unique effects on B cell homeostasis.
Identifiants
pubmed: 36776828
doi: 10.3389/fimmu.2023.1087986
pmc: PMC9908612
doi:
Substances chimiques
Janus Kinase Inhibitors
0
Immunomodulating Agents
0
Anti-Inflammatory Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1087986Informations de copyright
Copyright © 2023 Frede, Lorenzetti, Hüppe, Janowska, Troilo, Schleyer, Venhoff, Voll, Thiel, Venhoff and Rizzi.
Déclaration de conflit d'intérêts
NV: Speaker honoraria: AbbVie, Novartis, UCB, Bristol-Myers-Squibb, Pfizer; Advisory Boards: AbbVie, Novartis, UCB; Research grants: Bristol-Myers-Squibb, Novartis, Pfizer. JT: Speaker honoraria: GSK, BMS, Astra-Zeneca, Abbvie, UCB, Lilly; Advisory Boards: Novartis, GSK, Astra Zeneca, Lilly. Grant/research support from: BMS, Novartis. RV: Speaker fees: AbbVie, Amgen, BMS, Boehringer-Ingelheim, GSK, Janssen-Cilag, Hexal, Novartis, Pfizer, Roche; Advisory JAK inhibition modulates B-cell development boards: AbbVie, Amgen, Boehringer-Ingelheim, BMS, GSK, Janssen-Cilag, Hexal, Neutrolis, Novartis, Sanofi, Takeda; Unrestricted research grants: Amgen, BMS, Novartis, Pfizer. NF received travel grants from Pfizer, Janssen, Sobi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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