{"title":"Bruton's tyrosine kinase - A new target for immune mediated inflammatory diseases?","authors":"John D Isaacs","doi":"10.1016/j.semarthrit.2025.152681","DOIUrl":null,"url":null,"abstract":"<p><p>Bruton's tyrosine kinase (BTK) is a cytoplasmic protein that plays a key role in signalling pathways downstream of diverse surface receptors in B-cells and myeloid cells. These include the B-cell receptor itself, Fc receptors including FcεRI, toll-like receptors and chemokine receptors. Congenital deficiency of BTK causes X-linked agammaglobulinaemia because of B-cell developmental block, and BTK inhibitors (BTKi) are approved for the treatment of certain B-cell malignancies. They have also been studied in a variety of autoimmune and inflammatory diseases. In rheumatic conditions, results have been disappointing in rheumatoid arthritis (RA) and systemic lupus erythematosus but with some evidence for efficacy in Sjogren's syndrome. Data are more positive in multiple sclerosis, as well as in the cutaneous disease chronic spontaneous urticaria and possibly pemphigus vulgaris. BTKi may also find a role in severe allergic disease such as food allergy. First generation BTKi had a safety profile that included cardiotoxicity, hypertension, haemorrhage and rash. Second generation inhibitors have a more acceptable safety profile although dose-limiting toxicity is still observed in some conditions, including RA. Pharmacokinetic factors aside, the variable efficacy in different diseases is not fully explained but is likely to reflect disease dependence on different pathways in B-cells and myeloid cells and their relative sensitivity to BTKi.</p>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":" ","pages":"152681"},"PeriodicalIF":4.6000,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Seminars in arthritis and rheumatism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.semarthrit.2025.152681","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Bruton's tyrosine kinase (BTK) is a cytoplasmic protein that plays a key role in signalling pathways downstream of diverse surface receptors in B-cells and myeloid cells. These include the B-cell receptor itself, Fc receptors including FcεRI, toll-like receptors and chemokine receptors. Congenital deficiency of BTK causes X-linked agammaglobulinaemia because of B-cell developmental block, and BTK inhibitors (BTKi) are approved for the treatment of certain B-cell malignancies. They have also been studied in a variety of autoimmune and inflammatory diseases. In rheumatic conditions, results have been disappointing in rheumatoid arthritis (RA) and systemic lupus erythematosus but with some evidence for efficacy in Sjogren's syndrome. Data are more positive in multiple sclerosis, as well as in the cutaneous disease chronic spontaneous urticaria and possibly pemphigus vulgaris. BTKi may also find a role in severe allergic disease such as food allergy. First generation BTKi had a safety profile that included cardiotoxicity, hypertension, haemorrhage and rash. Second generation inhibitors have a more acceptable safety profile although dose-limiting toxicity is still observed in some conditions, including RA. Pharmacokinetic factors aside, the variable efficacy in different diseases is not fully explained but is likely to reflect disease dependence on different pathways in B-cells and myeloid cells and their relative sensitivity to BTKi.
期刊介绍:
Seminars in Arthritis and Rheumatism provides access to the highest-quality clinical, therapeutic and translational research about arthritis, rheumatology and musculoskeletal disorders that affect the joints and connective tissue. Each bimonthly issue includes articles giving you the latest diagnostic criteria, consensus statements, systematic reviews and meta-analyses as well as clinical and translational research studies. Read this journal for the latest groundbreaking research and to gain insights from scientists and clinicians on the management and treatment of musculoskeletal and autoimmune rheumatologic diseases. The journal is of interest to rheumatologists, orthopedic surgeons, internal medicine physicians, immunologists and specialists in bone and mineral metabolism.