Abstract:
:BTK and ITK are cytoplasmic tyrosine kinases of crucial importance for B and T cell development, with loss-of-function mutations causing X-linked agammaglobulinemia and susceptibility to severe, frequently lethal, Epstein-Barr virus infection, respectively. Over the last few years, considerable efforts have been made in order to develop small-molecule inhibitors for these kinases to treat lymphocyte malignancies, autoimmunity or allergy/hypersensitivity. The rationale is that even if complete lack of BTK or ITK during development causes severe immunodeficiency, inactivation after birth may result in a less severe phenotype. Moreover, therapy can be transient or only partially block the activity of BTK or ITK. Furthermore, a drug-induced B cell deficiency is treatable by gamma globulin substitution therapy. The newly developed BTK inhibitor PCI-32765, recently renamed Ibrutinib, has already entered several clinical trials for various forms of non-Hodgkin lymphoma as well as for multiple myeloma. Experimental animal studies have demonstrated highly promising treatment effects also in autoimmunity. ITK inhibitors are still under the early developmental phase, but it can be expected that such drugs will also become very useful. In this study, we present BTK and ITK with their signalling pathways and review the development of the corresponding inhibitors.
journal_name
Scand J Immunoljournal_title
Scandinavian journal of immunologyauthors
Vargas L,Hamasy A,Nore BF,Smith CIdoi
10.1111/sji.12069subject
Has Abstractpub_date
2013-08-01 00:00:00pages
130-9issue
2eissn
0300-9475issn
1365-3083journal_volume
78pub_type
杂志文章,评审abstract::A heterologous antiserum (antiserum 7420) against B-lymphocyte antigen(s) was raised in a rabbit by immunization with peripheral blood lymphocytes from a patient with chronic lymphocytic leukaemia (CLL). After absorptions with pooled normal human serum, IgA, IgD, and IgM M-components, the fluorescein isothiocyanate-co...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1979.tb01329.x
更新日期:1979-01-01 00:00:00
abstract::Strategically positioned in peripheral tissues, immune sentinel cells sense microbes and/or their shed products through different types of pattern-recognition receptors. Upon secretion, pre-formed pro-inflammatory mediators activate the microvasculature, inducing endothelium/neutrophil adherence and impairing endothel...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-3083.2007.01983.x
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abstract::Recently, associations were found between several autoimmune diseases and functional variants of interleukin-23 receptor (IL23R) gene; here, we studied the possible association of nine polymorphisms of IL23R with ankylosing spondylitis (AS) and with Sjögren syndrome (SS). In our study, we genotyped groups of patients ...
journal_title:Scandinavian journal of immunology
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doi:10.1111/j.1365-3083.2009.02265.x
更新日期:2009-07-01 00:00:00
abstract::Therapy with tumour necrosis factor-alpha (TNFalpha)-blocking agents is successful in treating inflammatory disorders, but carries an increased risk of manifest and reactivating infection with intracellular bacteria. In a mouse model of latent Salmonella typhimurium infection, neutralization of TNFalpha did not result...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.2007.01920.x
更新日期:2007-05-01 00:00:00
abstract::The immune system of a healthy individual responds vigorously to foreign microbial antigens. However, all potentially immunogenic regions (determinants) within an antigen are not functionally of equal relevance in mediating host immunity against the pathogen. Moreover, some of these antigenic determinants are well pro...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.2006.01891.x
更新日期:2007-02-01 00:00:00
abstract::Discontinuous Percoll gradients have been used to obtain selected human peripheral blood T lymphocytes without having to resort to interactions with immune complexes in the fractionation of Tm, Tg and Ta cells. Here, we could show that Ta cells represent a heterogeneous population with no distinct density profile, in ...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1982.tb00719.x
更新日期:1982-09-01 00:00:00
abstract::Antigen-binding peripheral blood leukocytes (PBL) from normal and bursectomized agammaglobulinemic chickens were labeled by incubation in vitro with radioiodinated antigen at 4 degrees C in the presence of sodium azide. [125I]TGAL-binding cells could be detected by autoradiography of PBL from normal, unimmunized chick...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1975.tb02612.x
更新日期:1975-01-01 00:00:00
abstract::Myasthenia gravis (MG) and its animal model experimental autoimmune MG (EAMG), are T-cell dependent, antibody-mediated autoimmune disorders. A dual altered peptide ligand (APL) composed of the tandemly arranged two single amino acids analogs of two myasthenogenic peptides, p195-212 and p259-271, was demonstrated to do...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.2007.01940.x
更新日期:2007-06-01 00:00:00
abstract::In a group of 20 patients with asymptomatic paraproteinemia, as judged after at least 3 years of follow-up, the primary and secondary antibody response to Helix pomatia hemocyanin (HPH) was defective as compared with the response in controls. The class of antibody was assessed by mercaptoethanol (ME) treatment of seru...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:
更新日期:1976-01-01 00:00:00
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1982.tb00680.x
更新日期:1981-05-01 00:00:00
abstract::Allergic airway disorders such as asthma and allergic rhinitis are mainly caused by inhaled allergen-induced improper activation and responses of immune and non-immune cells. One important response is the production of IL-27 by macrophages and dendritic cells (DCs) during the early stage of airway allergies. IL-27 exe...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章,评审
doi:10.1111/sji.12959
更新日期:2021-02-01 00:00:00
abstract::Secretagogin is a newly identified calcium-binding protein selectively expressed in neuroendocrine tissue and pancreatic beta-cells. The function of secretagogin is unknown, but it has been suggested in beta-cells to influence calcium-influx, insulin secretion and proliferation, and has been observed downregulated in ...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.2006.01854.x
更新日期:2006-12-01 00:00:00
abstract::G-protein-coupled receptors play a major role in the activation of the innate immune system, such as polymorphonuclear neutrophils. Members of the formyl peptide receptor family recognize chemotactic peptides as well the amyloïd-beta peptide and fragments of the human immunodeficiency virus envelope and may thus be im...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.2005.01651.x
更新日期:2005-08-01 00:00:00
abstract::Modified C-reactive protein (mCRP) has been reported to non-specifically bind to immunoglobulins; notwithstanding, the nature of these interactions is not clear. The aim of this study was to investigate the binding of antibodies directed against HSA and IgG to mCRP, fibrinogen (Fg), IgG, fibronectin (Fn) and C1q and i...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.2012.02704.x
更新日期:2012-07-01 00:00:00
abstract::Three strains of mice bearing the autosomal recessive lpr gene (MRL, C57BL/6, and C3H) that had spontaneously developed a lupus-like disease were studied sequentially for functional natural killer (NK) and natural cytotoxic (NC) cell activity. Natural killing was impaired in spleen and bone marrow cells from all the l...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1986.tb03073.x
更新日期:1986-04-01 00:00:00
abstract::Interleukin (IL)-12 has dominated the field of cell-mediated immunity since its discovery more than 10 years ago, and clearly plays an essential role in the development of Th1 cells under a variety of conditions. Recent studies now indicate that the importance of IL-12 is not limited to initiating an immune response, ...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-3083.2001.00917.x
更新日期:2001-06-01 00:00:00
abstract::To determine whether the genetic background of the insulin-producing beta cells of the pancreas contributes to autoimmune diabetes susceptibility, we have used a model of the disease based on transferring spleen cells from nonobese diabetic (NOD) <--> C57BL/6 (B6) embryo aggregation (EA) chimeras into B6 and NOD irrad...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1046/j.1365-3083.1998.00479.x
更新日期:1998-12-01 00:00:00
abstract::Several vaccination studies have been performed in monkeys and humans testing the feasibility of prophylactic and therapeutic immunizations against Helicobacter pylori. The monkey studies showed that immune responses were induced by oral vaccination with the mucosal adjuvant LT (Escherichia coli heat-labile enterotoxi...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-3083.2001.00911.x
更新日期:2001-05-01 00:00:00
abstract::The oral commensal bacterium Streptococcus gordonii has been gathering interest as a candidate live mucosal vaccine delivery vector. S. gordonii has been shown to be capable of activating antigen presenting immune cells in a manner which leads to their activation and maturation, yet the mechanism used by S. gordonii t...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.2009.02232.x
更新日期:2009-04-01 00:00:00
abstract::IgE antibodies against trinitrophenylated ovalbumin (TNP-OVA) were raised in Brown Norway rats by a highly reproducible immunization procedure. With these rats, the kinetics of the IgE response was studied, both for free circulating and cell-bound IgE. Cell-bound IgE was dissociated from peritoneal cell suspensions at...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1983.tb00760.x
更新日期:1983-01-01 00:00:00
abstract::Thirty-two mycobacterial components were detected by antibodies contained in leprosy patients' sera across the clinical spectrum and rabbit anti-M. leprae hyperimmune sera by western blot analysis of armadillo-derived M. leprae antigen preparations. Sera of borderline tuberculoid patients were found to contain antibod...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1987.tb02303.x
更新日期:1987-12-01 00:00:00
abstract::Sensitization of B10.A mice with oxazolone results in delayed-type hypersensitivity (DTH) and a two to three-fold increase in the weight of regional lymph nodes by the third day. Hydrocortisone treatment of the animals 3 days after sensitization suppresses the manifestation of DTH on the tenth day but not on the seven...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1978.tb00529.x
更新日期:1978-01-01 00:00:00
abstract::IgE levels in cord blood have been investigated as predictors of atopy, but no definitive findings have been made. Other factors, including cells and/or cytokines may serve as predictors of this disease. Cord blood and peripheral blood was obtained at birth and at 7 months of age, respectively, from children (n = 2) w...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.2008.02169.x
更新日期:2008-11-01 00:00:00
abstract::Rat AgB transplantation antigens were isolated after papain digestion of spleens from the inbred strain Hooded Lister. Both subunits of the AgB antigens were present in the purified material. Some physical characteristics of the antigens have been determined. An antiserum, raised in a rabbit, against the purified mate...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1980.tb00209.x
更新日期:1980-01-01 00:00:00
abstract::The authors have previously reported on the ability of A60, an immunodominant antigenic complex of Mycobacterium bovis BCG, to prevent cancer development in mice challenged with EMT 6 tumour cells. Such effect proved to rely on neoplastic cell lysis by cytolytic T lymphocytes and activated macrophages. The involvement...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1046/j.1365-3083.1996.d01-318.x
更新日期:1996-10-01 00:00:00
abstract::Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on a T-cell mediated activation of autoreactive B cells. However, it is still unclear if B cells can present CII to T cells. To investigate the role of B cells as antigen-presenting cells (APCs) for CII, we purified B cells from lymph nodes of ...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1046/j.1365-3083.2002.01071.x
更新日期:2002-04-01 00:00:00
abstract::The pair of microH-chain and kappa L-chain transgenes encoding the Sp6 TNP/DNA-specific IgM was bred onto the rearrangement-deficient genetic background of RAG-2T mice, and onto the kappa L-chain expression-deficient background of iE kappa T mice. Bone marrow of Sp6 transgenic RAG-2T mice contained normal numbers of B...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1995.tb03621.x
更新日期:1995-07-01 00:00:00
abstract::This study (1) analysed the percentage of γδ T cells, γδ T cell subsets, Th17 cells and regulatory T cells (Treg cells) and (2) determined the role of IL-23 in primary nephrotic syndrome (PNS) patients with active disease and in remission. Eighty-four patients with PNS and 51 healthy age-matched controls were included...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/sji.12629
更新日期:2018-01-01 00:00:00
abstract::Inflammatory mediators such as interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) exhibit local autocrine and paracrine effects as well as distant systemic effects on target cells. Human Kupffer cells, the fixed tissue macrophages of the liver, may modulate immune and en...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1991.tb02532.x
更新日期:1991-05-01 00:00:00
abstract::In these case reports, we investigated pandemic influenza 2009 vaccination of primary hypogammaglobulinaemic patients. Three combined variable immunodeficiency (CVID) patients and one X-linked agammaglobulinaemia (XLA) patient were vaccinated with the pandemic vaccine A/California/7/2009 (H1N1)-like split virus (X179a...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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更新日期:2011-08-01 00:00:00