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    397 results match your criteria Bruton Agammaglobulinemia

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    The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement.
    PLoS One 2017 19;12(4):e0175961. Epub 2017 Apr 19.
    Department of Molecular Medicine, Sapienza University of Rome, Roma, Italy.
    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). Read More

    Receptor-guided 3D-QSAR studies, molecular dynamics simulation and free energy calculations of Btk kinase inhibitors.
    BMC Syst Biol 2017 Mar 14;11(Suppl 2). Epub 2017 Mar 14.
    Department of Biomedical Sciences, College of Medicine, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju, 61452, Republic of Korea.
    Background: Bruton tyrosine kinase (Btk) plays an important role in B-cell development, differentiation, and signaling. It is also found be in involved in male immunodeficiency disease such as X-linked agammaglobulinemia (XLA). Btk is considered as a potential therapeutic target for treating autoimmune diseases and hematological malignancies. Read More

    Serial Serum Immunoglobulin G (IgG) Trough Levels in Patients with X-linked Agammaglobulinemia on Replacement Therapy with Intravenous Immunoglobulin: Its Correlation with Infections in Indian Children.
    J Clin Immunol 2017 Apr 21;37(3):311-318. Epub 2017 Mar 21.
    Division of Basic and Clinical Immunology, University of California, Irvine, CA, USA.
    Patients with primary antibody deficiency (PAD) are being increasingly diagnosed in the developing world. However, care of these children continues to remain suboptimal due to financial and social constraints. Immunoglobulin (Ig) trough level is an important predicting factor for infections in children on replacement immunoglobulin therapy. Read More

    X-linked agammaglobulinemia - first case with Bruton tyrosine kinase mutation from Pakistan.
    J Pak Med Assoc 2017 Mar;67(3):471-473
    Department of Paediatrics and Child Health, The Aga Khan University Hospital, Karachi, Pakistan.
    X-linked agammaglobulinemia (XLA) is a primary immunodeficiency with more than 600 mutations in Bruton tyrosine kinase (Bkt) gene which are responsible for early-onset agammaglobulinemia and repeated infections. Herein we present a case of a 3-year-old boy with history of repeated diarrhoea and an episode of meningoencephalitis with hemiplegia. The workup showed extremely low levels of immunoglobulin with low CD+19 cells. Read More

    Gastrointestinal Manifestations in X-linked Agammaglobulinemia.
    J Clin Immunol 2017 Apr 24;37(3):287-294. Epub 2017 Feb 24.
    Massachusetts General Hospital, Boston, MA, USA.
    Purpose: X-linked agammaglobulinemia is a primary humoral immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection. Although there is increased awareness of autoimmune and inflammatory complications in X-linked agammaglobulinemia (XLA), the spectrum of gastrointestinal manifestations has not previously been fully explored.

    Methods: We present a case report of a family with two affected patients with XLA. Read More

    Human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activity is regulated by and potentially targetable through Bruton tyrosine kinase.
    J Allergy Clin Immunol 2017 Feb 16. Epub 2017 Feb 16.
    Interfaculty Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany. Electronic address:
    Background: The Nod-like receptor NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and Bruton tyrosine kinase (BTK) are protagonists in innate and adaptive immunity, respectively. NLRP3 senses exogenous and endogenous insults, leading to inflammasome activation, which occurs spontaneously in patients with Muckle-Wells syndrome; BTK mutations cause the genetic immunodeficiency X-linked agammaglobulinemia (XLA). However, to date, few proteins that regulate NLRP3 inflammasome activity in human primary immune cells have been identified, and clinically promising pharmacologic targeting strategies remain elusive. Read More

    Discovery of a Potent BTK Inhibitor with a Novel Binding Mode by Using Parallel Selections with a DNA-Encoded Chemical Library.
    Chembiochem 2017 May 8;18(9):864-871. Epub 2017 Feb 8.
    X-Chem Pharmaceuticals, 100 Beaver Street, Waltham, MA, 02453, USA.
    We have identified and characterized novel potent inhibitors of Bruton's tyrosine kinase (BTK) from a single DNA-encoded library of over 110 million compounds by using multiple parallel selection conditions, including variation in target concentration and addition of known binders to provide competition information. Distinct binding profiles were observed by comparing enrichments of library building block combinations under these conditions; one enriched only at high concentrations of BTK and was competitive with ATP, and another enriched at both high and low concentrations of BTK and was not competitive with ATP. A compound representing the latter profile showed low nanomolar potency in biochemical and cellular BTK assays. Read More

    The NLRP3 inflammasome and bruton's tyrosine kinase in platelets co-regulate platelet activation, aggregation, and in vitro thrombus formation.
    Biochem Biophys Res Commun 2017 Jan 26;483(1):230-236. Epub 2016 Dec 26.
    Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany. Electronic address:
    Cleavage of interleukin-1β (IL-1β) is a key inflammatory event in immune cells and platelets, which is mediated by nucleotide-binding domain leucine rich repeat containing protein (NLRP3)-dependent activation of caspase-1. In immune cells, NLRP3 and caspase-1 form inflammasome complexes with the adaptor proteins apoptosis-associated speck-like protein containing a CARD (ASC) and bruton's tyrosine kinase (BTK). In platelets, however, the regulatory triggers and the functional effects of the NLRP3 inflammasome are unknown. Read More

    Frontline therapy and role of high-dose consolidation in mantle cell lymphoma.
    Hematology Am Soc Hematol Educ Program 2016 Dec;2016(1):419-424
    Department of Haematology, Derriford Hospital, Plymouth and Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom.
    Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin lymphoma. It is predominantly a disease of older individuals, with a median age at presentation of ∼70 years. For the majority of patients, the management revolves around immuno-chemotherapy often followed by maintenance rituximab, and at relapse, a range of options are available. Read More

    Bruton Tyrosine Kinase Inhibition Attenuates Liver Damage in a Mouse Warm Ischemia and Reperfusion Model.
    Transplantation 2017 Feb;101(2):322-331
    1 Division of Liver and Pancreas Transplantation, Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at University of California, Los Angeles, CA. 2 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA. 3 Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, CA. 4 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, CA.
    Background: Bruton tyrosine kinase (Btk) is a central player in multiple signaling pathways of lymphoid and myeloid cells. Myeloid cells are crucial early effectors in organ ischemia-reperfusion (IR) injury. BTKB66 is a selective, irreversible inhibitor of Btk. Read More

    [Clinic of humoral primary immunodeficiencies in adults. Experience in a tertiary hospital].
    Rev Alerg Mex 2016 Oct-Dec;63(4):334-341
    Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Hospital de Especialidades, Servicio de Alergia e Inmunología Clínica, Ciudad de México, México.
    Background: Primary immunodeficiencies (PID) are characterized by alteration of the components of the immune system. Humoral deficiencies represent 50%. The most common are selective IgA deficiency, Bruton agammaglobulinemia, and common variable immunodeficiency (CVID). Read More

    A Novel Aziridine-based Bruton's Tyrosine Kinase Inhibitor Induces Apoptosis Through Down-regulation of p65/RelA Phosphorylation on Serine 536 and ERK1/2 in Mantle Cell Lymphoma.
    Anticancer Res 2016 11;36(11):6133-6140
    Latvian Institute of Organic Synthesis, Riga, Latvia.
    Background: Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin's lymphoma characterized by hyperactive neoplastic B-cells and extended tumor cell survival. Bruton's tyrosine kinase (BTK), a crucial kinase in the B-cell antigen receptor signaling pathway, has emerged as a novel target of MCL therapy. A novel BTK-targeting inhibitor, JuSt-23F was prepared. Read More

    Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 production through the activation of Bruton's tyrosine kinase and STAT3.
    Virology 2017 Jan 25;500:96-102. Epub 2016 Oct 25.
    Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, 555 31st Street, Downers Grove, IL 60515, United States. Electronic address:
    Previous data demonstrate that Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 to promote the survival of LMP2A-expressing B cell lymphomas. Since STAT3 is an important regulator of IL-10 production, we hypothesized that LMP2A activates a signal transduction cascade that increases STAT3 phosphorylation to enhance IL-10. Using LMP2A-negative and -positive B cell lines, the data indicate that LMP2A requires the early signaling molecules of the Syk/RAS/PI3K pathway to increase IL-10. Read More

    Ibrutinib inhibition of Bruton protein-tyrosine kinase (BTK) in the treatment of B cell neoplasms.
    Pharmacol Res 2016 Nov 15;113(Pt A):395-408. Epub 2016 Sep 15.
    Blue Ridge Institute for Medical Research, 3754 Brevard Road, Suite 116, Box 19, Horse Shoe, NC 28742-8814, United States. Electronic address:
    The Bruton non-receptor protein-tyrosine kinase (BTK), a deficiency of which leads to X-linked agammaglobulinemia, plays a central role in B cell antigen receptor signaling. Owing to the exclusivity of this enzyme in B cells, the acronym could represent B cell tyrosine kinase. BTK is activated by the Lyn and SYK protein kinases following activation of the B cell receptor. Read More

    Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy.
    World J Gastroenterol 2016 Jul;22(28):6484-500
    Man Fai Law, Carmen KM Cheung, Lydia HP Tam, Karen Ma, Kent CY So, Bonaventure Ip, Jacqueline So, Jennifer Lai, Joyce Ng, Tommy HC Tam, Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China.
    Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Read More

    Shulman disease (eosinophilic fasciitis) in X-linked agammaglobulinemia.
    Pol J Pathol 2016 Jun;67(2):183-8
    Prof. Anna Pituch-Noworolska MD, Department of Clinical Immunology, Polish-American Institute of Pediatrics, Medical College, Jagiellonian University, Wielicka 265, 30-663 Krakow, Poland, tel./fax +48 12 658 17 56, e-mail:
    X-linked agammaglobulinemia (XLA) diagnosed in the first year of life is an immunodeficiency with a life-long indication for substitution of immunoglobulins, due to lack of B lymphocytes in the periphery. The decrease of bacterial infection frequency and severity is an effect of immunoglobulin replacement. However, in the majority of patients bronchiectasis and chronic sinusitis with an overgrown mucous membrane develop despite regular substitution. Read More

    Clinical characteristics and genetic profiles of 174 patients with X-linked agammaglobulinemia: Report from Shanghai, China (2000-2015).
    Medicine (Baltimore) 2016 Aug;95(32):e4544
    aDepartment of Allergy and Immunology, Shanghai Children's Medical Center bDivision of Immunology, Institute of Pediatric Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai cDepartment of Internal Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China dDivision of Allergy and Immunology, Department of Pediatrics, Virginia Commonwealth University, Richmond, VA.
    X-linked agammaglobulinemia (XLA) is a humoral primary immunodeficiency. XLA patients typically present with very low numbers of peripheral B cells and a profound deficiency of all immunoglobulin isotypes. Most XLA patients carry mutations in Bruton tyrosine kinase (BTK) gene. Read More

    Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.
    PLoS One 2016 19;11(7):e0159607. Epub 2016 Jul 19.
    Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
    Acalabrutinib (ACP-196) is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK) with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL). First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Read More

    From immune substitution to immunomodulation.
    Semin Hematol 2016 Apr 7;53 Suppl 1:S7-9. Epub 2016 Apr 7.
    Department of Pediatric Pulmonology and Immunology, Charité University Hospital, Berlin, Germany. Electronic address:
    Intravenous immunoglobulins (IVIGs) are currently used in many fields of medicine for replacement and immunomodulation. This review focuses on the milestones in the history of human immunoglobulins since the initial observation by Ogden C. Bruton who described replacement therapy in a boy with agammaglobulinemia. Read More

    Development of a Low-Cost Stem-Loop Real-Time Quantification PCR Technique for EBV miRNA Expression Analysis.
    Mol Biotechnol 2016 Sep;58(8-9):540-50
    Department of Public Health and Pediatric Sciences, Medical School, University of Turin, Turin, Italy.
    MicroRNAs (miRNAs) are short, single stranded, non-coding RNA molecules. They are produced by many different species and are key regulators of several physiological processes. miRNAs are also encoded by the genomes of multiple virus families, such as herpesvirus family. Read More

    [Primary hypogammaglobulinemia complicated with liver cirrhosis and literature review].
    Zhonghua Er Ke Za Zhi 2016 May;54(5):379-82
    Department of Gastroenterology, Shanghai Children's Medical Center, Shanghai Jiao Tong University Medical College, Shanghai 200127, China.
    Objective: To explore the pathogenesis, treatment and prognosis of primary hypogammaglobulinemia complicated with liver cirrhosis in a child.

    Method: Pathogenesis, treatment and prognosis of X-linked agammaglobulinemia (XLA ) complicated with liver cirrhosis in a child were analyzed in Shanghai Children's Medical Center.Using"primary hypogammaglobulinemia"and"liver cirrhosis"as keywords, literatures were searched from Pubmed and Chinese data of Weipu and Wanfang data from January 1988 to January 2015. Read More

    [X-linked agammaglobulinemia in adults. Clinical evolution].
    Medicina (B Aires) 2016 ;76(2):65-70
    Unidad Inmunología e Histocompatibilidad, Hospital Dr. Carlos G. Durand, Buenos Aires, Argentina.
    X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels and clinically by extracellular bacterial infections which mainly compromise the respiratory tract as well as recurrent diarrheas. The mainstay of treatment is gammaglobulin replacement therapy, which allows most patients to reach adulthood with high quality of life. We analyzed the clinical features of 14 patients over 18 years of age with XLA diagnosis that received treatment in our unit from the year 2003, the date the first patient was derived, until 2015. Read More

    [Shifting cellulitis in a patient with X-linked hypogammaglobulinemia].
    Ann Dermatol Venereol 2016 Jun-Jul;143(6-7):453-6. Epub 2016 Apr 11.
    Hôpital Pontchaillou, service de dermatologie, CHU de Rennes, 2, rue Henri-Le-Guilloux, 35000 Rennes, France; Université de Rennes 1, 2, avenue du Professeur-Léon-Bernard, 35043 Rennes cedex, France; Hôpital Pontchaillou, unité de pharmacoépidémiologie, CHU de Rennes, 2, rue Henri-Le-Guilloux, 35033 Rennes cedex 9, France.
    Background: In cases of immunodeficiency, a systemic infection may be revealed by atypical symptoms, particularly those involving the skin.

    Patients And Methods: The present case describes a 19-year-old male with X-linked hypogammaglobulinemia, or Bruton agammaglobulinemia, treated with intravenous immunoglobulin G antibodies. Over a 6-week period, the patient developed recurrent plaques in both legs, first on one and then on the other, without fever. Read More

    Bruton tyrosine kinase inhibition in chronic lymphocytic leukemia.
    Semin Oncol 2016 Apr 9;43(2):251-9. Epub 2016 Feb 9.
    The Ohio State University Comprehensive Cancer Center, Arthur G James Comprehensive Cancer Center, Columbus, OH.
    Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and remains incurable outside of the setting of allogeneic stem cell transplant. While the standard therapy for both initial and relapsed CLL has traditionally included monoclonal antibody therapy in combination with chemotherapy, there are patients with high-risk disease features including unmutated IgVH, del(11q22) and del(17p13) that are associated with poor overall responses to these therapies with short time to relapse and shortened overall survival. Additionally, many of these therapies have a high rate of infectious toxicity in a population already at increased risk. Read More

    Helicobacter cinaedi bacteremia resulting from antimicrobial resistance acquired during treatment for X-linked agammaglobulinemia.
    J Infect Chemother 2016 Oct 31;22(10):704-6. Epub 2016 Mar 31.
    Division of Infectious Diseases, Tokyo Metropolitan Children's Medical Center, Japan.
    This is the first report of penicillin/cephalosporin-resistant Helicobacter cinaedi arising from prolonged treatment. H. cinaedi, common among immunocompromised patients, caused recurrent bacteremia and cellulitis in a 19-year-old Japanese man with X-linked agammaglobulinemia. Read More

    Hair and Nail Changes During Long-term Therapy With Ibrutinib for Chronic Lymphocytic Leukemia.
    JAMA Dermatol 2016 Jun;152(6):698-701
    Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
    Importance: Ibrutinib, a Bruton tyrosine kinase inhibitor, is a new targeted agent approved by the US Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma, and Waldenström macroglobulinemia. Ibrutinib is overall well tolerated but long-term treatment is required until disease progression or intolerable toxic effects occur. Little is known regarding its cutaneous adverse effects. Read More

    Clinical and mutational features of X-linked agammaglobulinemia in Mexico.
    Clin Immunol 2016 Apr 4;165:38-44. Epub 2016 Mar 4.
    Unidad de Investigación en Inmunodeficiencias, Instituto Nacional de Pediatría, SSA, México, DF, Mexico.
    X-linked agammaglobulinemia (XLA) is caused by BTK mutations, patients typically show <2% of peripheral B cells and reduced levels of all immunoglobulins; they suffer from recurrent infections of bacterial origin; however, viral infections, autoimmune-like diseases, and an increased risk of developing gastric cancer are also reported. In this work, we report the BTK mutations and clinical features of 12 patients diagnosed with XLA. Furthermore, a clinical revision is also presented for an additional cohort of previously reported patients with XLA. Read More

    Ibrutinib for treatment of chronic lymphocytic leukemia.
    Am J Health Syst Pharm 2016 Mar;73(6):367-75
    Division of Hematology, Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Solove Research Institute, Columbus, OH.
    Purpose: The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of ibrutinib are described.

    Summary: Ibrutinib is a first-in-class oral inhibitor of Bruton tyrosine kinase (BTK) approved for treatment of relapsed chronic lymphocytic leukemia (CLL). Ibrutinib blocks downstream signaling of the B-cell receptor, disrupting stromal microenvironment interactions and B-cell cytokine signaling. Read More

    Interfering with baffled B cells at the lupus tollway: Promises, successes, and failed expectations.
    J Allergy Clin Immunol 2016 May 4;137(5):1325-33. Epub 2016 Mar 4.
    Division of Immunology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa. Electronic address:
    B cells play an important role in systemic lupus erythematosus by acting not only as precursors of autoantibody-producing cells but also as antigen-presenting, cytokine-secreting, and regulatory cells. Unopposed activation of B cells through their B-cell receptor for antigen, as seen in B cells lacking Lyn kinase, results in systemic autoimmunity. The B-cell activating factor of the TNF family (BAFF), nucleic acid-sensing Toll-like receptors (TLRs), and type I interferon can affect B-cell survival and decrease their threshold for activation. Read More

    X-Linked Agammagobulinemia in a Large Series of North African Patients: Frequency, Clinical Features and Novel BTK Mutations.
    J Clin Immunol 2016 Apr 1;36(3):187-94. Epub 2016 Mar 1.
    Clinical Immunology Unit, Ibn Rochd Hospital, King Hassan II University-AinChok, Casablanca, Morocco.
    Purpose: X-linked agammagobulinemia (XLA) is a primary immunodeficiency caused by Bruton's tyrosine kinase (BTK) gene defect. XLA patients have absent or reduced number of peripheral B cells and a profound deficiency in all immunoglobulin isotypes. This multicenter study reports the clinical, immunological and molecular features of Bruton's disease in 40 North African male patients. Read More

    Targeting protein kinase C in mantle cell lymphoma.
    Br J Haematol 2016 May 23;173(3):394-403. Epub 2016 Feb 23.
    Institute of Pathology, University of Würzburg and Comprehensive Cancer Center (CCC) Mainfranken, Würzburg, Germany.
    Although targeting the Bruton tyrosine kinase (BTK) with ibrutinib has changed lymphoma treatment, patients with mantle cell lymphoma (MCL) remain incurable. In this study, we characterized a broad range of MCL cell lines and primary MCL cells with respect to the response to the BTK inhibitor, ibrutinib, and compared it with the response to the protein kinase C (PKC) inhibitor, sotrastaurin. At clinically relevant concentrations, each drug induced potent cell death only in the REC-1 cell line, which was accompanied by robust inhibition of AKT and ERK1/ERK2 (ERK1/2, also termed MAPK3/MAPK1) phosphorylation. Read More

    Cohort of Iranian Patients with Congenital Agammaglobulinemia: Mutation Analysis and Novel Gene Defects.
    Expert Rev Clin Immunol 2016 24;12(4):479-86. Epub 2016 Feb 24.
    a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.
    Objectives: Impairment in early B-cell development can cause a predominantly antibody deficiency with severe depletion of peripheral B-cells. Mutations in the gene encoding for Bruton's-tyrosine-kinase (BTK) and the components of the pre-B-cell receptor complex or downstream signaling molecules have been related to this defect in patients with agammaglobulinemia.

    Methods: Iranian patients with congenital agammaglobulinemia were included and the correlation between disease-causing mutations and parameters such as clinical and immunologic phenotypes were evaluated in available patients. Read More

    X-linked Agammaglobulinemia.
    Indian J Pediatr 2016 Apr 24;83(4):331-7. Epub 2016 Feb 24.
    Pediatric Allergy and Immunology Unit, Department of Pediatrics, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
    X-linked agammaglobulinemia (XLA) is one of the commonest primary immune deficiencies encountered in pediatric clinical practice. In adults, common variable immunodeficiency (CVID) is the most common primary immunodeficiency disease (PID). It is an X-linked disorder characterized by increased susceptibility to encapsulated bacteria, severe hypergammaglobulinemia and absent circulating B cells in the peripheral blood. Read More

    Allogeneic stem cell transplantation for X-linked agammaglobulinemia using reduced intensity conditioning as a model of the reconstitution of humoral immunity.
    J Hematol Oncol 2016 Feb 13;9. Epub 2016 Feb 13.
    Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya City, Hyogo, 663-8501, Japan.
    Background: We herein report the first case of X-linked agammaglobulinemia (XLA) that underwent allogeneic stem cell transplantation using reduced intensity conditioning (RIC). We chronologically observed the reconstitution of humoral immunity in this case.

    Case Presentation: The patient was a 28-year-old Japanese male with XLA who previously had life-threatening infectious episodes and was referred for the possible indication of allogeneic stem cell transplantation. Read More

    Inhibition of the Bruton Tyrosine Kinase Pathway in B-Cell Lymphoproliferative Disorders.
    Cancer J 2016 Jan-Feb;22(1):34-9
    From the Bing Center for Waldenström's Macroglobulinemia and Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
    Activation of the Bruton tyrosine kinase (BTK) pathway plays an important role in the pathophysiology of a number of B-cell lymphoproliferative disorders (LPDs). A number of preclinical studies support inhibiting BTK as a mechanism to treat LPDs. Clinically, BTK inhibitors, specifically ibrutinib, have shown to be safe and effective on treating patients with indolent B-cell lymphomas and chronic lymphocytic leukemia (CLL). Read More

    Eosinophilic gastroenteritis in a patient with Bruton's tyrosine kinase deficiency.
    Pediatr Int 2016 May 3;58(5):417-419. Epub 2016 Feb 3.
    Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
    Eosinophilic gastrointestinal diseases (EGID) are relatively rare diseases characterized by eosinophilic infiltration of the gastrointestinal tract resulting in various gastrointestinal symptoms. EGID are often caused by allergic reactions or systemic eosinophilic disorders, but their comorbidity with Bruton's tyrosine kinase (BTK) deficiency has not been previously documented. Here, we report a case of eosinophilic gastroenteritis (EG) in a patient with BTK deficiency. Read More

    Btk inhibition treats TLR7/IFN driven murine lupus.
    Clin Immunol 2016 Mar 25;164:65-77. Epub 2016 Jan 25.
    TIP Immunology, EMD Serono Research and Development Institute, 45A Middlesex Turnpike, Billerica, MA 01821, USA.
    Bruton's tyrosine kinase (Btk) is expressed in a variety of immune cells and previous work has demonstrated that blocking Btk is a promising strategy for treating autoimmune diseases. Herein, we utilized a tool Btk inhibitor, M7583, to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. In BXSB-Yaa lupus mice, Btk inhibition reduced autoantibodies, nephritis, and mortality. Read More

    Ibrutinib as a Bruton Kinase Inhibitor in the Management of Chronic Lymphocytic Leukemia: A New Agent With Great Promise.
    Clin Lymphoma Myeloma Leuk 2016 Feb 22;16(2):63-9. Epub 2015 Nov 22.
    Department of Hematology and Oncology, Oakland University, William Beaumont School of Medicine, William Beaumont Health System, Royal Oak, MI.
    The recent discovery of the role of the B-cell antigen receptor (BCR) signaling pathway in the propagation and maintenance of both normal B-cell function and in B-cell malignancies has highlighted the importance of many protein kinases involved in BCR signal propagation. Considerable research attention has focused on the Bruton tyrosine kinase (BTK) as a potential therapeutic target in B-cell malignancies. Treatment paradigms including ibrutinib, a potent inhibitor of the BTK recently approved by the US Food and Drug Administration, have significantly improved disease outcome among high-risk and relapsed/refractory cases of chronic lymphocytic leukemia. Read More

    Ibrutinib for mantle cell lymphoma.
    Future Oncol 2016 Feb 13;12(4):477-91. Epub 2016 Jan 13.
    Department of Haematology, Plymouth Hospitals NHS Trust, Plymouth, UK.
    Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin lymphoma. Ibrutinib is a first-in-class, oral inhibitor of Bruton's tyrosine kinase which acts by downstream inhibition of the B-cell receptor. Early clinical trials have demonstrated excellent tolerability and a modest side-effect profile in relapsed/refractory MCL. Read More

    Bruton Tyrosine Kinase-Dependent Immune Cell Cross-talk Drives Pancreas Cancer.
    Cancer Discov 2016 Mar 29;6(3):270-85. Epub 2015 Dec 29.
    Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon. Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
    Unlabelled: Pancreas ductal adenocarcinoma (PDAC) has one of the worst 5-year survival rates of all solid tumors, and thus new treatment strategies are urgently needed. Here, we report that targeting Bruton tyrosine kinase (BTK), a key B-cell and macrophage kinase, restores T cell-dependent antitumor immune responses, thereby inhibiting PDAC growth and improving responsiveness to standard-of-care chemotherapy. We report that PDAC tumor growth depends on cross-talk between B cells and FcRγ(+) tumor-associated macrophages, resulting in T(H)2-type macrophage programming via BTK activation in a PI3Kγ-dependent manner. Read More

    Molecular modeling studies on series of Btk inhibitors using docking, structure-based 3D-QSAR and molecular dynamics simulation: a combined approach.
    Arch Pharm Res 2016 Mar 23;39(3):328-39. Epub 2015 Dec 23.
    Department of Biomedical Sciences, College of Medicine, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju, 501-759, Republic of Korea.
    Bruton tyrosine kinase (Btk) is a non-receptor tyrosine kinase. It is a crucial component in BCR pathway and expressed only in hematopoietic cells except T cells and Natural killer cells. BTK is a promising target because of its involvement in signaling pathways and B cell diseases such as autoimmune disorders and lymphoma. Read More

    Efficacy and safety of Gammaplex(®) 5% in children and adolescents with primary immunodeficiency diseases.
    Clin Exp Immunol 2016 May 15;184(2):228-36. Epub 2016 Feb 15.
    Rush University Medical Center, Chicago, IL, USA.
    This open-label multi-centre study evaluated Gammaplex(®) 5%, a human intravenous immunoglobulin (IVIG) 5% liquid, in 25 children and adolescent patients (aged 3-16 years) with primary immunodeficiency diseases (PIDs). Subjects received Gammaplex 5% (at doses of 300-800 mg/kg/infusion) for 12 months, with a 3-month follow-up. The primary efficacy end-point was the incidence of serious acute bacterial infections (SABIs) during the 12-month treatment period. Read More

    Oral administration of Bruton's tyrosine kinase inhibitors impairs GPVI-mediated platelet function.
    Am J Physiol Cell Physiol 2016 Mar 9;310(5):C373-80. Epub 2015 Dec 9.
    Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, Portland, Oregon; Department of Cell, Developmental & Cancer Biology, School of Medicine, Oregon Health & Science University, Portland, Oregon; and Division of Hematology and Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, Oregon.
    The Tec family kinase Bruton's tyrosine kinase (Btk) plays an important signaling role downstream of immunoreceptor tyrosine-based activation motifs in hematopoietic cells. Mutations in Btk are involved in impaired B-cell maturation in X-linked agammaglobulinemia, and Btk has been investigated for its role in platelet activation via activation of the effector protein phospholipase Cγ2 downstream of the platelet membrane glycoprotein VI (GPVI). Because of its role in hematopoietic cell signaling, Btk has become a target in the treatment of chronic lymphocytic leukemia and mantle cell lymphoma; the covalent Btk inhibitor ibrutinib was recently approved by the US Food and Drug Administration for treatment of these conditions. Read More

    PROTECTIVE LEVELS OF VARICELLA-ZOSTER ANTIBODY DID NOT EFFECTIVELY PREVENT CHICKENPOX IN AN X-LINKED AGAMMAGLOBULINEMIA PATIENT.
    Rev Inst Med Trop Sao Paulo 2015 Sep-Oct;57(5):455-7
    Departmento de Pediatria, Universidade Federal de São Paulo, São Paulo, SP, Brasil,
    We describe the case of an eight-year-old boy with X-linked agammaglobulinemia who developed mild varicella despite regular intravenous immunoglobulin (IVIG) therapy. He maintained protective antibody levels against varicella and the previous batches of IVIG that he received had adequate varicella-specific IgG levels. The case illustrates that IVIG may not prevent VZV infection. Read More

    A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies.
    Blood 2016 Jan 5;127(4):411-9. Epub 2015 Nov 5.
    Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'Hématologie, Pierre-Bénite, Université Claude Bernard Lyon 1, Lyon, France;
    We report the results of a multicenter phase 1 dose-escalation study of the selective Bruton tyrosine kinase (BTK) inhibitor ONO/GS-4059 in 90 patients with relapsed/refractory B-cell malignancies. There were 9 dose-escalation cohorts ranging from 20 mg to 600 mg once daily with twice-daily regimens of 240 mg and 300 mg. Twenty-four of 25 evaluable chronic lymphocytic leukemia (CLL) patients (96%) responded to ONO/GS-4059, with a median treatment duration of 80 weeks; 21 CLL patients remain on treatment. Read More

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