The DOI matches its Crossref record; 135 of the 136 references it cites were found in a registry or an index.
The role of Bruton’s tyrosine kinase in autoimmunity and implications for therapy
Open accessAbstract
Bruton's tyrosine kinase (BTK) mediates B cell signaling and is also present in innate immune cells but not T cells. BTK propagates B cell receptor (BCR) responses to antigen-engagement as well as to stimulation via CD40, toll-like receptors (TLRs), Fc receptors (FCRs) and chemokine receptors. Importantly, BTK can modulate signaling, acting as a "rheostat" rather than an "on-off" switch; thus, overexpression leads to autoimmunity while decreased levels improve autoimmune disease outcomes. Autoreactive B cells depend upon BTK for survival to a greater degree than normal B cells, reflected as loss of autoantibodies with maintenance of total antibody levels when BTK is absent. This review describes contributions of BTK to immune tolerance, including studies testing BTK-inhibitors for treatment of autoimmune diseases.
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“Importantly, BTK transduces constitutive signaling downstream of the BCR in many B-cell malignancies, so BTK has long been considered an attractive target for treating these diseases.”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [1]
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Cites
Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia
Byrd, J. C., Furman, R. R., Coutre, S. E., Flinn, I. W., Burger, J. A., Blum, K. A., Grant, B., Sharman, J. P., Coleman, M., Wierda, W. G., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215637 · Cited by 2,270
Predominant Autoantibody Production by Early Human B Cell Precursors
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Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia
Tsukada, S., Saffran, D. C., Rawlings, D. J., Parolini, O., Allen, R. C., Klisak, I. J., Sparkes, R. S., Kubagawa, H., Mohandas, T. K., Quan, S. G., et al. (1993) · Cell · doi:10.1016/0092-8674(93)90667-f · Cited by 1,326
Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib
Woyach, J. A., Furman, R. R., Liu, T.-M., Ozer, H. G., Zapatka, M., Ruppert, A. S., Xue, L., Li, D. H.-H., Steggerda, S. M., Versele, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400029 · Cited by 1,275 · cited 4×
“Antigen-BCR binding triggers a signaling pathway in which BTK is recruited to the cell membrane from the cytosol, docks with the linker protein BLNK and phosphorylates PLCγ2, with downstream calcium flux and cellular activation via nuclear translocation of transcription factors NFκB and NFAT.”
InfluentialAdvani, R. H., Buggy, J. J., Sharman, J. P., Smith, S. M., Boyd, T. E., Grant, B., Kolibaba, K. S., Furman, R. R., Rodriguez, S., Chang, B. Y., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.42.7906 · Cited by 1,128 · cited 17×
“Thus, unlike other methods of targeting B lymphocytes, BTK inhibitors hold promise for improving B cell-related autoimmunity without inducing the degree of immunodeficiency seen in XLA.”
InfluentialLam, K., Kühn, R., & Rajewsky, K. (1997) · Cell · doi:10.1016/s0092-8674(00)80373-6 · Cited by 1,101
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Didona, D., Maglie, R., Eming, R., & Hertl, M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01418 · Cited by 266
Bruton tyrosine kinase degradation as a therapeutic strategy for cancer
Dobrovolsky, D., Wang, E. S., Morrow, S., Leahy, C., Faust, T., Nowak, R. P., Donovan, K. A., Yang, G., Li, Z., Fischer, E. S., et al. (2019) · Blood · doi:10.1182/blood-2018-07-862953 · Cited by 169
Mechanism-based criteria to improve therapeutic outcomes in progressive multiple sclerosis
Yong, H. Y. F., & Yong, V. W. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00581-x · Cited by 170
Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia
Kuter, D. J., Efraim, M. E., Mayer, J., Trněný, M., McDonald, V., Bird, R. J., Regenbogen, T., Garg, M., Kaplan, Z., Tzvetkov, N., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2110297 · Cited by 157
Metadata
- Authors
- Crofford, L. J., Nyhoff, L. E., Sheehan, J. H., & Kendall, P. L.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Crofford, Leslie J.
- Venue
- Expert Review of Clinical Immunology
- Publisher
- Informa UK Limited
- Published
- 2016-03-04
- Volume
- 12
- Issue
- 7
- Pages
- 763-773
- ISSN
- 1744-666X (ISSN-L)
- 1744-8409
- PMC
- PMC5070917
- OpenAlex
- W2258682798
- Cited by
- 142
- References
- 136
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 13 · 2023: 18 · 2022: 29 · 2021: 21 · 2020: 9 · 2019: 13 · 2018: 8 · 2017: 5 · 2016: 2
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Expert Review of Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (NIAMS R01 AR049010, NIDDK R01 DK84246)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- Bruton's tyrosine kinase, autoimmunity, B cell signaling, B cell receptor signaling, CD40 signaling, Toll-like receptors, Fc receptors, chemokine receptors, autoreactive B cells, autoantibodies, immune tolerance, BTK inhibitors, autoimmune disease therapy
- MeSH terms
- Agammaglobulinaemia Tyrosine Kinase, Animals, Anti-Inflammatory Agents, Autoantibodies, Autoimmune Diseases, B-Lymphocytes, Humans, Immune Tolerance, Lymphocyte Activation, Protein-Tyrosine Kinases, Receptors, Antigen, B-Cell, Signal Transduction, Autoimmunity
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