ArticleRheumatology (Oxford, England)2019
Evidence for enhanced Bruton's tyrosine kinase activity in transitional and naïve B cells of patients with granulomatosis with polyangiitis.
Article in Rheumatology (Oxford, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Aberrant B cell receptor signaling responses in circulating double-negative 2 B cells from radiographic axial spondyloarthritis patients.Journal of translational autoimmunity · 2025Article
- Targeting B cells and plasma cells in autoimmune diseases: From established treatments to novel therapeutic approaches.European journal of immunology · 2023Review
- Combination treatment with telitacicept, cyclophosphamide and glucocorticoids for severe Granulomatous polyangiitis: a case report and literature review.Frontiers in immunology · 2023Review
- Human B-cell subset identification and changes in inflammatory diseases.Clinical and experimental immunology · 2022Review
- Review
- Src-related thrombocytopenia: a fine line between a megakaryocyte dysfunction and an immune-mediated disease.Blood advances · 2022Article
- Decreased BAFF Receptor Expression and Unaltered B Cell Receptor Signaling in Circulating B Cells from Primary Sjögren's Syndrome Patients at Diagnosis.International journal of molecular sciences · 2022Article
- Article
- B Lineage Cells in ANCA-Associated Vasculitis.International journal of molecular sciences · 2021Review
- Loss of immune homeostasis in patients with idiopathic pulmonary arterial hypertension.Thorax · 2021Article
- Bruton's Tyrosine Kinase Inhibition as an Emerging Therapy in Systemic Autoimmune Disease.Drugs · 2021Review
- Aberrant B Cell Receptor Signaling in Naïve B Cells from Patients with Idiopathic Pulmonary Fibrosis.Cells · 2021Article
- B Cell Activation and Escape of Tolerance Checkpoints: Recent Insights from Studying Autoreactive B Cells.Cells · 2021Review
- ANCA-Associated Vasculitis: An Update.Journal of clinical medicine · 2021Review
- Targeting Bruton's Tyrosine Kinase in Inflammatory and Autoimmune Pathologies.Frontiers in cell and developmental biology · 2021Review
- Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo determine Bruton's tyrosine kinase (BTK) protein and phosphorylation levels in B cell subsets of granulomatosis with polyangiitis (GPA) patients and to investigate the effect of BTK blockade on in vitro B cell cytokine production, subset distribution and (auto)antibody production.
methodsBTK protein and phosphorylation levels were determined by flow cytometry in peripheral blood B cells of 29 untreated GPA patients [9 active and 20 remission GPA patients (10 ANCA- and 10 ANCA+)], 9 age- and sex-matched healthy controls (HCs) and 9 untreated active RA patients. The effect of BTK blockade on in vitro B cell cytokine production, subset distribution and (auto)antibody production was determined in the same donors in peripheral blood mononuclear cell cultures.
resultsBTK protein levels were significantly increased in transitional and naïve B cells of active GPA and RA patients compared with remission GPA patients and HCs. Both B cell subsets of active patients were more sensitive to B cell receptor stimulation, as BTK and phospholipase Cγ2 phosphorylation were increased in these patients. In vitro BTK blockade had profound effects on B cell cytokine production, plasma cell formation and (auto)antibody production in both GPA patients and HCs. Interestingly, the effect of BTK blockade was less pronounced in active GPA patients, possibly due to increased activation of B cells.
conclusionWe show that BTK protein and phosphorylation levels are most profoundly increased in newly emerging B cells of active GPA patients compared with remission patients. BTK blockade greatly inhibits in vitro B cell effector functions in GPA patients and HCs. These promising data identify BTK as an interesting novel therapeutic target in the treatment of GPA.
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