ArticleArthritis research & therapy2020
Inhibition of effector B cells by ibrutinib in systemic sclerosis.
Article in Arthritis research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Autoantibody landscape and functional role of anti-C-C motif chemokine receptor 8 autoantibodies in systemic sclerosis: post-hoc analysis of a B-cell depletion trial.Nature communications · 2025Trial
- The B-cells paradigm in systemic sclerosis: an update on pathophysiology and B-cell-targeted therapies.Clinical and experimental immunology · 2025Review
- BTK inhibitor ibrutinib reduces LPS-induced inflammation in C8-B4 microglia.EXCLI journal · 2025Article
- Review
- Effector and regulatory B-cell imbalance in systemic sclerosis: cooperation or competition?Clinical rheumatology · 2024Review
- Targeting Bruton's tyrosine kinase (BTK) as a signaling pathway in immune-mediated diseases: from molecular mechanisms to leading treatments.Advances in rheumatology (London, England) · 2024Review
- Method for Detecting Pathology of Internal Organs Using Bioelectrography.Diagnostics (Basel, Switzerland) · 2024Article
- B-cells in pulmonary arterial hypertension: friend, foe or bystander?The European respiratory journal · 2024Review
- Impact of ibrutinib on inflammation in a mouse model of Graves' orbitopathy.Frontiers in endocrinology · 2024Article
- The role of immune cells in the pathogenesis of connective tissue diseases-associated pulmonary arterial hypertension.Frontiers in immunology · 2024Review
- Pervasive aggregation and depletion of host and viral proteins in response to cysteine-reactive electrophilic compounds.bioRxiv : the preprint server for biology · 2023Article
- Anti-topoisomerase 1 Antibody Level Changes after B Cell Depletion Therapy in Systemic Sclerosis.Doklady. Biochemistry and biophysics · 2023Article
- Novel Therapeutic Strategies in the Treatment of Systemic Sclerosis.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Therapeutic Approaches to Systemic Sclerosis: Recent Approvals and Future Candidate Therapies.Clinical reviews in allergy & immunology · 2023Review
- A quinazoline derivative suppresses B cell hyper-activation and ameliorates the severity of systemic lupus erythematosus in mice.Frontiers in pharmacology · 2023Article
- The mosaic of autoimmunity - Finally discussing in person. The 13Autoimmunity reviews · 2022Article
- Autoantibodies as Biomarker and Therapeutic Target in Systemic Sclerosis.Biomedicines · 2022Review
- Bruton's Kinase Inhibitors for the Treatment of Immunological Diseases: Current Status and Perspectives.Journal of clinical medicine · 2022Review
- Pathogenetic Aspects of Systemic Sclerosis: A View Through the Prism of B Cells.Frontiers in immunology · 2022Review
- Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
objectiveSystemic sclerosis (SSc) is a connective tissue disease with a significant morbidity and reduced survival of patients. Effective treatment and clinical control of the disease remain challenging. In particular, the development of pulmonary and cardiac fibrosis and pulmonary hypertension are severe complications responsible for excessive mortality. Currently available treatment strategies only alleviate symptoms and slow disease progression. Here, we investigated the therapeutic potential of ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor used in B cell malignancies, to alter B cell pathology in SSc in an in vitro model of autoimmunity.
methodsPBMCs and sorted B cells of 24 patients with SSc were used for functional testing after stimulation with hypomethylated DNA fragments (CpG) to induce an innate immune response. The effects of ibrutinib on cytokine production, autoantibody release, and activation of the transcription factor NFκB were evaluated.
resultsIbrutinib was able to reduce the production of the profibrotic hallmark cytokines IL-6 and TNF-α mainly from the effector B cell population in patients with SSc. Importantly, small doses of ibrutinib (0.1 μM) preserved the production of immunoregulatory IL-10 while effectively inhibiting hyperactivated, profibrotic effector B cells. In a flow cytometry analysis of phosphorylated NFκB, an important transcription factor in the induction of innate immune responses in B cells, significantly less activation was observed with ibrutinib treatment.
conclusionOur data could pave the avenue for a clinical application of ibrutinib for patients with SSc as a novel treatment option for the underlying pathogenetic immune imbalance contributing to disease onset and progression.
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