ArticleJCI insight2022
Human T-bet+ B cell development is associated with BTK activity and suppressed by evobrutinib.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Efficacy and safety results after >3.5 years of treatment with the Bruton's tyrosine kinase inhibitor evobrutinib in relapsing multiple sclerosis: Long-term follow-up of a Phase II randomised clinical trial with a cerebrospinal fluid sub-study.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024Trial
- Interferon-Mediated Regulation of Memory B Cell Identity and Function.Immunological reviews · 2026Review
- Review
- Integrin β1 Demarks Precursors of Brain-Residing Antibody-Secreting Cells in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Investigations of remibrutinib in models pertinent to multiple sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- B-cell abundance in perivascular cuffs associates with local lesion activity in multiple sclerosis.Acta neuropathologica communications · 2026Article
- Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders.Current neuropharmacology · 2026Review
- Primary Progressive Multiple Sclerosis: New Therapeutic Approaches.Neuropsychopharmacology reports · 2025Review
- The regulatory functions of G protein-coupled receptors signaling pathways in B cell differentiation and development contributing to autoimmune diseases.Cell & bioscience · 2025Review
- Review
- T-bet+ CXCR3+ B cells drive hyperreactive B-T cell interactions in multiple sclerosis.Cell reports. Medicine · 2025Article
- Aggressive treatment of early acute focal inflammatory activity to extend the window for BTK inhibition in multiple sclerosis.Therapeutic advances in neurological disorders · 2025Review
- Review
- Targeting T-bet expressing B cells for therapeutic interventions in autoimmunity.Clinical and experimental immunology · 2024Review
- Twin study dissects CXCR3Med (New York, N.Y.) · 2024Article
- The Role of CXCR3 in Nervous System-Related Diseases.Mediators of inflammation · 2024Review
- Antibody response to SARS-CoV-2 vaccines in patients with relapsing multiple sclerosis treated with evobrutinib: A Bruton's tyrosine kinase inhibitor.Multiple sclerosis (Houndmills, Basingstoke, England) · 2023Article
- Bruton tyrosine kinase inhibitors for multiple sclerosis.Nature reviews. Neurology · 2023Review
- The Immunomodulatory Functions of BTK Inhibition in the Central Nervous System.Journal of inflammation research · 2022Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent clinical trials have shown promising results for the next-generation Bruton's tyrosine kinase (BTK) inhibitor evobrutinib in the treatment of multiple sclerosis (MS). BTK has a central role in signaling pathways that govern the development of B cells. Whether and how BTK activity shapes B cells as key drivers of MS is currently unclear. Compared with levels of BTK protein, we found higher levels of phospho-BTK in ex vivo blood memory B cells from patients with relapsing-remitting MS and secondary progressive MS compared with controls. In these MS groups, BTK activity was induced to a lesser extent after anti-IgM stimulation. BTK positively correlated with CXCR3 expression, both of which were increased in blood B cells from clinical responders to natalizumab (anti-VLA-4 antibody) treatment. Under in vitro T follicular helper-like conditions, BTK phosphorylation was enhanced by T-bet-inducing stimuli, IFN-γ and CpG-ODN, while the expression of T-bet and T-bet-associated molecules CXCR3, CD21, and CD11c was affected by evobrutinib. Furthermore, evobrutinib interfered with in vitro class switching, as well as memory recall responses, and disturbed CXCL10-mediated migration of CXCR3+ switched B cells through human brain endothelial monolayers. These findings demonstrate a functional link between BTK activity and disease-relevant B cells and offer valuable insights into how next-generation BTK inhibitors could modulate the clinical course of patients with MS.
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Registered trials
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.