675 results match your criteria Bruton Agammaglobulinemia


[Intravenous immunoglobulin replacement therapy in 114 cases of congenital agammaglobulinemia].

Zhonghua Er Ke Za Zhi 2021 Jun;59(6):495-500

Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Developmental and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing 400014, China.

To analyze the clinical characteristics of congenital agammaglobulinemia and the efficacy of intravenous immunoglobulin (IVIG) replacement therapy for this disease. The basic characteristics, clinical manifestations, laboratory examinations, and outcomes of 114 patients with congenital agammaglobulinemia diagnosed in Children's Hospital of Chongqing Medical University from January 1988 to April 2020 were retrospectively analyzed. The efficacy of IVIG in improving the clinical symptoms between regular and irregular treatment groups were compared by χ test. Read More

View Article and Full-Text PDF

Crohn's-like Enteritis in X-Linked Agammaglobulinemia: A Case Series and Systematic Review.

J Allergy Clin Immunol Pract 2021 May 21. Epub 2021 May 21.

Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

Background: X-linked agammaglobulinemia (XLA) is an inherited primary immunodeficiency that usually manifests clinically with recurrent sinopulmonary infections. Gastrointestinal manifestations are mostly driven by acute infections and disturbed mucosal immunity, but there is a notable prevalence of inflammatory bowel disease (IBD). Differentiating between XLA-associated enteritis, which can originate from recurrent infections, and IBD can be diagnostically and therapeutically challenging. Read More

View Article and Full-Text PDF

X-linked agammaglobulinemia: ınvestigation of clinical and laboratory findings, novel gene mutations and prevention of ınfective complications in long-term follow-up.

Am J Clin Exp Immunol 2021 15;10(1):37-43. Epub 2021 Feb 15.

Department of Pediatric Immunology, Ege University Faculty of Medicine Izmir, Turkey.

Introduction-Objective: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease predominantly with antibody deficiency and characterized by recurrent pyogenic infections, absence of B cells and agammaglobulinemia. In this study, it is aimed to review the demographic data of our XLA patients and examine the frequency of severe bacterial and mild infections and benefits of immunoglobulin replacement therapies to reduce the rate of infections. In addition, correlations between genotypic results and clinical and laboratory findings were searched. Read More

View Article and Full-Text PDF
February 2021

Effective, safe, and sustained correction of murine XLA using a UCOE-BTK promoter-based lentiviral vector.

Mol Ther Methods Clin Dev 2021 Mar 20;20:635-651. Epub 2021 Jan 20.

Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA 98101, USA.

X-linked agammaglobulinemia (XLA) is an immune disorder caused by mutations in Bruton's tyrosine kinase (). BTK is expressed in B and myeloid cells, and its deficiency results in a lack of mature B cells and protective antibodies. We previously reported a lentivirus (LV) BTK replacement therapy that restored B cell development and function in and double knockout mice (a phenocopy of human XLA). Read More

View Article and Full-Text PDF

Possible COVID-19 reinfection in a patient with X-linked agammaglobulinaemia.

BMJ Case Rep 2021 Mar 4;14(3). Epub 2021 Mar 4.

Respiratory Medicine, Liverpool Heart and Chest Hospital, Liverpool, UK.

This report highlights the case of a patient with X-linked agammaglobulinaemia (XLA) and resultant bronchiectasis who was discharged from hospital after recovering from real-time reverse transcriptase-PCR positive COVID-19 infection having had a subsequent negative swab and resolution of symptoms, but was readmitted 3 weeks later with recrudescent symptoms and a further positive swab. Although there are reports of COVID-19 infection in XLA, for the first time we report a case of possible reinfection. Lessons learnt from this case include the potential for reinfection of COVID-19 in a patient with a weakened immune system and the importance of repeating COVID-19 swabs in inpatients. Read More

View Article and Full-Text PDF

X-Linked Agammaglobulinemia With Chronic Meningoencephalitis: A Diagnostic Challenge.

Indian Pediatr 2021 Feb;58(2):169-173

Department of Radiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

X-linked agammaglobulinemia (XLA) is a primary disorder of humoral immunity characterized by Bruton tyrosine kinase gene mutations resulting in a primary antibody deficiency. While an intact T-cell function largely protects against majority of viral infections, enteroviruses are notorious for infecting these patients due to impaired mucosal immunity. Although the incidence of enteroviral meningoencephalitis in XLA is only 1-5%, yet the mortality is quite high. Read More

View Article and Full-Text PDF
February 2021

Ublituximab plus ibrutinib versus ibrutinib alone for patients with relapsed or refractory high-risk chronic lymphocytic leukaemia (GENUINE): a phase 3, multicentre, open-label, randomised trial.

Lancet Haematol 2021 Apr 22;8(4):e254-e266. Epub 2021 Feb 22.

Sarah Cannon Research Institute, Nashville, TN, USA.

Background: Patients with chronic lymphocytic leukaemia and high-risk features have poorer outcomes on ibrutinib than those without high-risk features. The aim of this study was to assess the benefit of adding ublituximab, an anti-CD20 monoclonal antibody, to ibrutinib therapy in this population.

Methods: We did a randomised, phase 3, multicentre study (GENUINE) of patients aged 18 years or older with relapsed or refractory chronic lymphocytic leukaemia with at least one of 17p deletion, 11q deletion, or TP53 mutation, at 119 clinics in the USA and Israel. Read More

View Article and Full-Text PDF

The role of ibrutinib in COVID-19 hyperinflammation: A case report.

Int J Infect Dis 2021 Apr 16;105:274-276. Epub 2021 Feb 16.

Department of Haematology, Imperial College Healthcare and NHS Trust Hammersmith Hospital, 72 Du Cane Rd, London, W12 0HS, United Kingdom.

Immune modulation in COVID-19 is emerging as an important therapeutic strategy as increasing evidence suggests that inflammatory pathways are implicated in lung damage. Bruton tyrosine kinase inhibitors (BTKi), such as ibrutinib, are commonly used to treat indolent B-cell neoplasms and chronic graft-versus-host disease (GvHD). Given their potential to suppress pulmonary inflammatory cytokines and lessen acute lung injury, this could be applicable in the context of hospitalised COVID-19 patients. Read More

View Article and Full-Text PDF

Skin cancer in congenital X-linked agammaglobulinaemia.

BMJ Case Rep 2021 Feb 5;14(2). Epub 2021 Feb 5.

Internal Medicine, Hospital de Braga, Braga, Portugal.

View Article and Full-Text PDF
February 2021

BTK gatekeeper residue variation combined with cysteine 481 substitution causes super-resistance to irreversible inhibitors acalabrutinib, ibrutinib and zanubrutinib.

Leukemia 2021 05 1;35(5):1317-1329. Epub 2021 Feb 1.

Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 86, Huddinge, Sweden.

Irreversible inhibitors of Bruton tyrosine kinase (BTK), pioneered by ibrutinib, have become breakthrough drugs in the treatment of leukemias and lymphomas. Resistance variants (mutations) occur, but in contrast to those identified for many other tyrosine kinase inhibitors, they affect less frequently the "gatekeeper" residue in the catalytic domain. In this study we carried out variation scanning by creating 11 substitutions at the gatekeeper amino acid, threonine 474 (T474). Read More

View Article and Full-Text PDF

Acalabrutinib: a highly selective, potent Bruton tyrosine kinase inhibitor for the treatment of chronic lymphocytic leukemia.

Leuk Lymphoma 2021 05 11;62(5):1066-1076. Epub 2021 Jan 11.

Department of Lymphoid Malignancies, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Poland.

Inhibiting the activity of Bruton tyrosine kinase (BTK) prevents the activation of the B-cell receptor (BCR) signaling pathway, which in turn prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. Acalabrutinib is an orally available, highly selective, next-generation inhibitor of BTK. Based on the results of two key phase 3 trials (ELEVATE-TN in patients with previously untreated chronic lymphocytic leukemia [CLL] and ASCEND in patients with relapsed or refractory CLL), which demonstrated superior progression-free survival while maintaining favorable tolerability, acalabrutinib was granted US Food and Drug Administration (FDA) approval in 2019 for the treatment of patients with CLL. Read More

View Article and Full-Text PDF

Relevance of the Bruton Tyrosine Kinase as a Target for COVID-19 Therapy.

Mol Cancer Res 2021 04 16;19(4):549-554. Epub 2020 Dec 16.

FoodLab, Faculty of Health Sciences, Universitat Oberta de Catalunya, Barcelona, Spain.

The outbreak of the novel coronavirus disease 2019 (COVID-19) has emerged as one of the biggest global health threats worldwide. As of October 2020, more than 44 million confirmed cases and more than 1,160,000 deaths have been reported globally, and the toll is likely to be much higher before the pandemic is over. There are currently little therapeutic options available and new potential targets are intensively investigated. Read More

View Article and Full-Text PDF

Zanubrutinib for the treatment of Waldenström Macroglobulinemia.

Expert Rev Hematol 2020 12 9;13(12):1303-1310. Epub 2020 Dec 9.

Department of Haematology, Peter MacCallum Cancer Centre , Melbourne, Australia.

: Waldenström Macroglobulinaemia (WM) is a heterogeneous, incurable condition which often relapses after chemoimmunotherapy. Novel therapies such as Bruton tyrosine-kinase (BTK) inhibitors have shown to be efficacious in treating WM but with an established, significant toxicity profile seen in the first-generation inhibitor Ibrutinib. Zanubrutinib is a selective, potent BTK inhibitor with the potential to reduce toxicity and improve efficacy. Read More

View Article and Full-Text PDF
December 2020

Atypical course of COVID-19 in patient with Bruton agammaglobulinemia.

J Infect Dev Ctries 2020 11 30;14(11):1248-1251. Epub 2020 Nov 30.

Faculty of Medicine, University of Belgrade, Serbia.

We present atypical course of the novel coronavirus disease (COVID-19) in 34-year man with Bruton agammaglobulinemia. The patient was successfully treated by a combination of available drugs, including convalescent plasma and interleukin-6 (IL-6) inhibitor. Read More

View Article and Full-Text PDF
November 2020

Management of Waldenström macroglobulinemia in 2020.

Hematology Am Soc Hematol Educ Program 2020 12;2020(1):372-379

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.

The management of Waldenström macroglobulinemia (WM) has evolved tremendously with recent genomic discoveries that correlate with clinical presentation and could help to tailor treatment approaches. The current diagnosis of WM requires clinicopathological criteria, including bone marrow involvement by lymphoplasmacytic lymphoma cells, a serum immunoglobulin M (IgM) monoclonal paraprotein, and presence of the MYD88 L265P mutation. Once the diagnosis is established, the relationship between the patient's symptoms and WM should be carefully investigated, because therapy should be reserved for symptomatic patients. Read More

View Article and Full-Text PDF
December 2020

Managing toxicities of Bruton tyrosine kinase inhibitors.

Hematology Am Soc Hematol Educ Program 2020 12;2020(1):336-345

Columbia University Medical Center, New York, NY.

Inhibition of Bruton's tyrosine kinase (BTK) has revolutionized the treatment landscape for patients with chronic lymphocytic leukemia (CLL). By targeting this critical kinase in proximal B-cell receptor signaling, BTK inhibitors (BTKis) impair cell proliferation, migration, and activation of NF-κB. Clinically, because indefinite inhibition is a mainstay of therapy, there is an extended period of exposure in which adverse effects can develop. Read More

View Article and Full-Text PDF
December 2020

CXCR4 in Waldenström's Macroglobulinema: chances and challenges.

Leukemia 2021 02 3;35(2):333-345. Epub 2020 Dec 3.

Institute of Experimental Cancer Research, CCC and University Hospital Ulm, Germany, 89081, Ulm, Germany.

It is one of the major aims in cancer research to improve our understanding of the underlying mechanisms which initiate and maintain tumor growth and to translate these findings into novel clinical diagnostic and therapeutic concepts with the ultimate goal to improve patient care. One of the greater success stories in this respect has been Waldenström's Macroglobulinemia (WM), which is an incurable B-cell neoplasm characterized by serum monoclonal immunoglobulin M (IgM) and clonal lymphoplasmacytic cells infiltrating the bone marrow. Recent years have succeeded to describe the molecular landscape of WM in detail, highlighting two recurrently mutated genes, the MYD88 and the CXCR4 genes: MYD88 with an almost constant and recurrent point mutation present in over 90% of patients and CXCR4 with over 40 different mutations in the coding region affecting up to 40% of patients. Read More

View Article and Full-Text PDF
February 2021

Ecthyma gangrenosum due to Pseudomonas aeruginosa sepsis as initial manifestation of X-linked agammaglobulinemia: a case report.

BMC Pediatr 2020 12 1;20(1):540. Epub 2020 Dec 1.

Intensive Care Unit, Key Medical Laboratory of Pediatrics, Key Laboratory of Child Development and Disorders, Chongqing Health Bureau, Ministry of Education, Children's Hospital of Chongqing Medical University, 136#, Zhong Shan 2nd Rord, Yuzhong District, Chongqing, People's Republic of China.

Background: X-linked agammaglobulinemia (XLA, OMIM#300,300), caused by mutations in the Bruton tyrosine kinase (BTK) gene, is a rare monogenic inheritable immunodeficiency disorder. Ecthyma gangrenosum is a cutaneous lesion caused by Pseudomonas aeruginosa that typically occurs in patients with XLA and other immunodeficiencies.

Case Presentation: We report the case of a 20-month-old boy who presented with fever, vomiting, diarrhea, and ecthyma gangrenosum. Read More

View Article and Full-Text PDF
December 2020

Vedolizumab is safe and effective in the treatment of X-linked agammaglobulinemia-associated inflammatory bowel disease.

J Allergy Clin Immunol Pract 2021 02 28;9(2):1006-1007. Epub 2020 Nov 28.

Department of Immunology, Perth Children's Hospital, Perth, WA, Australia; Department of Immunopathology, PathWest, Perth, WA, Australia. Electronic address:

View Article and Full-Text PDF
February 2021

Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines.

Blood 2021 01;137(2):185-189

Hematology Branch, National Heart, Lung, and Blood Institute.

Vaccinations are effective in preventing infections; however, it is unknown if patients with chronic lymphocytic leukemia (CLL) who are treatment naïve (TN) or receiving Bruton tyrosine kinase inhibitors (BTKi's) respond to novel adjuvanted vaccines. Understanding the effect of BTKi's on humoral immunity is timely because BTKi's are widely used and vaccination against coronavirus disease 2019 is urgently needed. In 2 open-label, single-arm clinical trials, we measured the effect of BTKi's on de novo immune response against recombinant hepatitis B vaccine (HepB-CpG) and recall response against recombinant zoster vaccine (RZV) in CLL patients who were TN or on BTKi. Read More

View Article and Full-Text PDF
January 2021

Human Inborn Errors of Immunity (HIEI): predominantly antibody deficiencies (PADs): if you suspect it, you can detect it.

J Pediatr (Rio J) 2021 Mar-Apr;97 Suppl 1:S67-S74. Epub 2020 Nov 24.

Universidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Médicas, Centro de Investigação em Pediatria, Departamento de Pediatria, Divisão de Alergia e Imunologia Pediátricas, Campinas, SP, Brazil. Electronic address:

Objective: This minireview gathers the scientific foundations of the literature on genetic errors in the development of the humoral immune system to help pediatricians suspect these defects.

Sources: A systemic search using the PubMed MEDLINE database was performed for all Predominantly Antibody Deficiencies (PADs) described in the 2020 IUIS Expert Committee for PID classification system, combined with terms for hypogammaglobulinemia. Search terms for PADs were based on the listed names and affected genes as classified by the IUIS 2020. Read More

View Article and Full-Text PDF

Presentation of a case of Bruton type primary agammaglobulinemia in Guinea.

Pan Afr Med J 2020 31;36:385. Epub 2020 Aug 31.

Neurology Department, Ignace Deen University Hospital Center, Conakry, Guinea.

X-linked agammaglobulinemia (XLA) is a rare genetic disease caused by a mutation in the Bruton tyrosine kinase (BTK) gene. It is characterized by a profound deficiency of B cells and a decrease in all classes of immunoglobulins (Ig). We report one case in a 3-year-old boy seen for recurrent acute otitis media, perineal abscess, oligoarthritis. Read More

View Article and Full-Text PDF
January 2021

Differential impact of BTK active site inhibitors on the conformational state of full-length BTK.

Elife 2020 11 23;9. Epub 2020 Nov 23.

Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, United States.

Bruton's tyrosine kinase (BTK) is targeted in the treatment of B-cell disorders including leukemias and lymphomas. Currently approved BTK inhibitors, including Ibrutinib, a first-in-class covalent inhibitor of BTK, bind directly to the kinase active site. While effective at blocking the catalytic activity of BTK, consequences of drug binding on the global conformation of full-length BTK are unknown. Read More

View Article and Full-Text PDF
November 2020

Case Report: A Case of X-Linked Agammaglobulinemia With High Serum IgE Levels and Allergic Rhinitis.

Front Immunol 2020 5;11:582376. Epub 2020 Nov 5.

Department of Pediatrics, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.

X-linked Agammaglobulinemia (XLA) is a rare genetic disorder of B-lymphocyte differentiation, characterized by the absence or paucity of circulating B cells, markedly reduced levels of all serum immunoglobulin isotypes and lack of specific antibody production. Bruton Tyrosine Kinase () gene encodes a cytoplasmic tyrosine kinase involved in the B cell maturation and its mutation, blocking B cell differentiation at the pre-B cell stage, and is responsible for XLA. All domains may be affected by the mutation, and the many genotypes are associated with a wide range of clinical presentations. Read More

View Article and Full-Text PDF
November 2020

Inhibition of Bruton tyrosine kinase by acalabrutinib dampens lipopolysaccharide/galactosamine-induced hepatic damage.

Biomed Pharmacother 2020 Nov 17;131:110736. Epub 2020 Sep 17.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.

Bruton tyrosine kinase (BTK) sits at the crossroads of adaptive and innate immunities. Nevertheless, the detailed role of BTK activation in hepatic inflammatory disorders is still elusive to date. Accordingly, we investigated the impact of blocking BTK activation by acalabrutinib (ACB) on lipopolysaccharide/galactosamine (LPS/D-GaIN)-induced deleterious manifestations in the liver. Read More

View Article and Full-Text PDF
November 2020

Inhibition of Bruton's Tyrosine Kinase Suppresses Cancer Stemness and Promotes Carboplatin-induced Cytotoxicity Against Bladder Cancer Cells.

Anticancer Res 2020 Nov;40(11):6093-6099

Translational Cell Therapy Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.

Background/aim: Bruton's tyrosine kinase (BTK) has been discovered to serve a critical role in the survival and infiltration of B-cell lymphoma. Recently, it was reported that BTK inhibitors exerted potential beneficial effects against numerous types of solid tumor, including glioblastoma multiforme and breast cancer; however, whether BTK is crucial for the progression of bladder cancer (BLCA) remains unclear. The present study investigated the in vitro function of BTK in stemness properties of BLCA cells. Read More

View Article and Full-Text PDF
November 2020

Fatal Progressive Meningoencephalitis Diagnosed in Two Members of a Family With X-Linked Agammaglobulinemia.

Front Pediatr 2020 18;8:579. Epub 2020 Sep 18.

Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Chronic enteroviral meningoencephalitis is a well-known complication in patients with X-linked agammaglobulinemia (XLA). However, progressive neurodegenerative disorders or chronic neuroinflammatory diseases with no causative microorganisms have been recognized as rare central nervous system (CNS) complications in XLA. We herein report a family in which two of three members with XLA had developed progressive meningoencephalitis with an unknown etiology. Read More

View Article and Full-Text PDF
September 2020

Distinct Clinical Features and Novel Mutations in Taiwanese Patients With X-Linked Agammaglobulinemia.

Front Immunol 2020 4;11:2001. Epub 2020 Sep 4.

Division of Allergy, Asthma, and Rheumatology, Chang Gung University College of Medicine, Taoyuan, Taiwan.

X-linked agammaglobulinemia (XLA) is caused by a mutation of the Bruton's tyrosine kinase () gene and is the most common genetic mutation in patients with congenital agammaglobulinemia. The aim of this study was to analyze the clinical features, genetic defects, and/or expression in patients suspected of having XLA who were referred from the Taiwan Foundation of Rare Disorders (TFRD). Patients with recurrent bacterial infections in the first 2 years of life, serum IgG/A/M below 2 standard deviations of the normal range, and ≦2% CD19+B cells were enrolled during the period of 2004-2019. Read More

View Article and Full-Text PDF

Three patients with X-linked agammaglobulinemia hospitalized for COVID-19 improved with convalescent plasma.

J Allergy Clin Immunol Pract 2020 Nov - Dec;8(10):3594-3596.e3. Epub 2020 Sep 15.

Icahn School of Medicine at Mount Sinai, Division of Allergy and Clinical Immunology, Departments of Medicine and Pediatrics, New York, NY. Electronic address:

View Article and Full-Text PDF
November 2020