ArticleArthritis & rheumatology (Hoboken, N.J.)2016
Bruton's Tyrosine Kinase Deficiency Inhibits Autoimmune Arthritis in Mice but Fails to Block Immune Complex-Mediated Inflammatory Arthritis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Bruton's Tyrosine Kinase (BTK) Inhibitors and Autoimmune Diseases: Making Sense of BTK Inhibitor Specificity Profiles and Recent Clinical Trial Successes and Failures.Frontiers in immunology · 2021Pooled it
- Targeting Bruton's Tyrosine Kinase (BTK) in Autoimmunity: Achievements, Opportunities and Challenges.Drug design, development and therapy · 2026Review
- 2025 update on clinical trials in immune thrombocytopenia.American journal of hematology · 2024Review
- Novel therapeutics and future directions for refractory immune thrombocytopenia.British journal of haematology · 2023Review
- Autoimmunity in Primary Immunodeficiencies (PID).Clinical reviews in allergy & immunology · 2023Review
- Review
- Bruton's Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis.Frontiers in immunology · 2022Article
- Targeting Bruton's Tyrosine Kinase in Inflammatory and Autoimmune Pathologies.Frontiers in cell and developmental biology · 2021Review
- T-B Lymphocyte Interactions Promote Type 1 Diabetes Independently of SLAM-Associated Protein.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Efficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disease Models.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- New Perspectives in Rheumatology: May You Live in Interesting Times: Challenges and Opportunities in Lupus Research.Arthritis & rheumatology (Hoboken, N.J.) · 2017Article
- Reply.Arthritis & rheumatology (Hoboken, N.J.) · 2017Article
- Bruton's Tyrosine Kinase, a Component of B Cell Signaling Pathways, Has Multiple Roles in the Pathogenesis of Lupus.Frontiers in immunology · 2017Review
- The role of Bruton's tyrosine kinase in autoimmunity and implications for therapy.Expert review of clinical immunology · 2016Review
- Mechanism-Based Strategies for the Management of Autoimmunity and Immune Dysregulation in Primary Immunodeficiencies.The journal of allergy and clinical immunology. In practiceReview
Corrections and comments
- Commented on byReply.2017
- Commented on by
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveBruton's tyrosine kinase (BTK) is a B cell signaling protein that also contributes to innate immunity. BTK inhibitors prevent autoimmune arthritis but have off-target effects, and the mechanisms of protection remain unknown. We undertook these studies using genetic deletion to investigate the role of BTK in adaptive and innate immune responses that drive inflammatory arthritis.
methodsBTK-deficient K/BxN mice were generated to study the role of BTK in a spontaneous model that requires both adaptive and innate immunity. The K/BxN serum-transfer model was used to bypass the adaptive system and elucidate the role of BTK in innate immune contributions to arthritis.
resultsBTK deficiency conferred disease protection to K/BxN mice, confirming outcomes of BTK inhibitors. B lymphocytes were profoundly reduced, more than in other models of BTK deficiency. Subset analysis revealed loss of B cells at all developmental stages. Germinal center B cells were also decreased, with downstream effects on numbers of follicular helper T cells and greatly reduced autoantibodies. In contrast, total IgG was only mildly decreased. Strikingly, and in contrast to small molecule inhibitors, BTK deficiency had no effect in the serum-transfer model of arthritis.
conclusionBTK contributes to autoimmune arthritis primarily through its role in B cell signaling and not through innate immune components.
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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.