Bruton's tyrosine kinase—an integral protein of B cell development that also has an essential role in the innate immune system

López‐Herrera, Gabriela; Vargas-Hernández, Alexander; González-Serrano, María Edith; Berrón-Ruíz, Laura; Rodríguez-Alba, Juan Carlos; Espinosa-Rosales, Francisco; Santos-Argumedo, Leopoldo

doi:10.1189/jlb.0513307

Cited by 90 publications

(92 citation statements)

References 88 publications

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“…Previous studies on patients with XLA [7–9] showed the involvement of BTK in innate immune cell responses [48] and its role in human DC responses upon TLR9 engagement [49]. Moreover, studies on the immune function of XLA patients who lack functional BTK might also provide information concerning the consequences of drugs acting as BTK inhibitors on innate immunity of patients under these new treatments [50–54].…”

Section: Discussionmentioning

confidence: 99%

The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement

et al. 2017

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The lack of BTK in X-linked agammaglobulinemia (XLA) patients does not affect monocytes and polymorphonuclear cells (PMN) phenotype and functions. In this study, we show that XLA patients had an increased frequency of the intermediate monocytes subset and that BTK-deficient monocytes and PMN had a normal expression of receptors involved in the activation and cellular responses. We demonstrate that BTK is not required for migration, phagocytosis and the production of reactive oxygen species (ROS) following engagement of FC gamma receptors (FcγR). XLA monocytes and PMN showed an efficient calcium (Ca2+)-independent activation of oxidative burst, suggesting that oxidative burst is less dependent by Ca2+ mobilization. The phagocytosis was functional and it remained unaltered also after Ca2+ chelation, confirming the independence of phagocytosis on Ca2+ mobilization. Intravenous immunoglobulin (IVIg) infusion exerted an anti-inflammatory effect by reducing the frequency of pro-inflammatory monocytes. In monocytes, the IVIg reduce the oxidative burst and phagocytosis even if these functions remained efficient.

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Section: Discussionmentioning

confidence: 99%

The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement

et al. 2017

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“…Infiltrating CD8+ T cells can be seen on joint cytology (87). Underlying mechanisms of T cell-driven autoimmunity (90) and/or innate immune hyperactivation (91, 92) have been proposed. In these cases, IVIG alone can be insufficient management (87, 90), progression despite methotrexate has been described (87), nonsteroidal anti-inflammatories (NSAIDs) may provide some benefit (89, 90), and there is no systematic guidance for the use of T cell or innate immune targeted strategies to date.…”

Section: Treatment Of Rheumatologic Disease In Primary Immunodeficmentioning

confidence: 99%

Mechanism-Based Strategies for the Management of Autoimmunity and Immune Dysregulation in Primary Immunodeficiencies

Walter

Farmer

Foldvari

et al. 2016

The Journal of Allergy and Clinical Immunology: In Practice

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A broad spectrum of autoimmunity is now well described in patients with primary immunodeficiencies (PIDs). Management of autoimmune disease in the background of PID is particularly challenging given the seemingly discordant goals of immune support and immune suppression. Our growing ability to define the molecular underpinnings of immune dysregulation has facilitated novel targeted therapeutics. This review focuses on mechanism-based treatment strategies for the most common autoimmune and inflammatory complications of PID including autoimmune cytopenias, rheumatologic disease, and gastrointestinal disease. We aim to provide guidance regarding the rational use of these agents in the complex PID patient population.

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“…BTK is a member of the cytoplasmic non-receptor tyrosine kinase family of TEC kinases, predominantly expressed in hematopoietic cells. BTK plays a key role in the B-cell receptor signaling pathway and is a mediator of proinflammatory signals [16]. Inhibition of BTK is a promising strategy for the treatment of B-cell malignancies and autoimmune disease [17,18].…”

Section: Introductionmentioning

confidence: 99%

Ibrutinib (ImbruvicaTM) potently inhibits ErbB receptor phosphorylation and cell viability of ErbB2-positive breast cancer cells

Grabinski

Ewald

2014

Invest New Drugs

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Ibrutinib (formerly PCI-32765) is a specific, irreversible, and potent inhibitor of Burton's tyrosine kinase (BTK) developed for the treatment of several forms of blood cancer. It is now an FDA-approved drug marketed under the name Imbruvica(TM) (Pharmacyclics, Inc.) and successfully used as an orally administered second-line drug in the treatment of mantle cell lymphoma. Since BTK is predominantly expressed in hematopoietic cells, the sensitivity of solid tumor cells to Ibrutinib has not been analyzed. In this study, we determined the effect of Ibrutinib on breast cancer cells. We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines. Treatment with Ibrutinib significantly reduced the viability of ErbB2+ cell lines with IC50 values at nanomolar concentrations, suggesting therapeutic potential of Ibrutinib in breast cancer. Combined treatment with Ibrutinib and the dual PI3K/mTOR inhibitor BEZ235 synergistically reduces cell viability of ErbB2+ breast cancer cells. Combination indices below 0.25 at 50% inhibition of cell viability were determined by the Chou-Talalay method. Therefore, the combination of Ibrutinib and canonical PI3K pathway inhibitors could be a new and effective approach in the treatment of breast cancer with activated ErbB receptors. Ibrutinib could thus become a valuable component of targeted therapy in aggressive ErbB2+ breast cancer.

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Bruton's tyrosine kinase—an integral protein of B cell development that also has an essential role in the innate immune system

Cited by 90 publications

References 88 publications

The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement

The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement

Mechanism-Based Strategies for the Management of Autoimmunity and Immune Dysregulation in Primary Immunodeficiencies

Ibrutinib (ImbruvicaTM) potently inhibits ErbB receptor phosphorylation and cell viability of ErbB2-positive breast cancer cells

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