816 results match your criteria Bruton Agammaglobulinemia


Changes in the BTK/NF-κB signaling pathway and related cytokines in different stages of neuromyelitis optica spectrum disorders.

Eur J Med Res 2022 Jun 21;27(1):96. Epub 2022 Jun 21.

Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People's Republic of China.

Objective: Neuromyelitis optica spectrum disorders (NMOSDs) are blindness-causing neuritis; their pathogenesis is still not fully elucidated. Although it has been determined that Bruton tyrosine kinase (BTK) and NF-κB are associated with NMOSD, the changes that occur in different periods remain unknown. The study aimed to demonstrate the changes in the BTK/NF-κB pathway and related chemokines in different stages of NMOSDs. Read More

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T Cell Abnormalities in X-Linked Agammaglobulinaemia: an Updated Review.

Clin Rev Allergy Immunol 2022 Jun 16. Epub 2022 Jun 16.

Allergy Immunology Unit, Department of Paediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

X-linked agammaglobulinaemia (XLA) is a primary immunodeficiency (PID) resulting from a defect in the B cell development. It has conventionally been thought that T cells play a major role in the development and function of the B cell compartment. However, it has also been shown that B cells and T cells undergo bidirectional interactions and B cells also influence the structure and function of the T cell compartment. Read More

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SOHO State of the Art Updates and Next Questions | Management of Most Difficult Cases of Chronic Lymphocytic Leukemia: Relapse After Both BTK and BCL2 Inhibition and Richter Transformation.

Authors:
John M Burke

Clin Lymphoma Myeloma Leuk 2022 Jul 22;22(7):427-435. Epub 2022 Apr 22.

Rocky Mountain Cancer Centers, Aurora, CO. Electronic address:

The introduction of targeted therapies in chronic lymphocytic leukemia (CLL) has ushered in a new era in which patients achieve better control of their disease, survive longer, and experience fewer toxicities than before. Despite this progress, a subgroup of patients with CLL will develop resistance to both Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 inhibitors. In addition, a subgroup of CLL cases will transform into aggressive lymphoma - called Richter transformation - either before or during targeted therapy. Read More

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Low prevalence of doravirine-associated resistance mutations among polish human immunodeficiency-1 (HIV-1)-infected patients.

Antivir Ther 2021 05 20;26(3-5):69-78. Epub 2021 Oct 20.

Department of Infectious, Tropical Diseases and Immune Deficiency, 175603Pomeranian Medical University in Szczecin, Szczecin, Poland.

Introduction: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) that retains activity against common NNRTI resistance mutations. In this study, we aimed to investigate the prevalence of DOR resistance mutations compared with that of resistance mutations for other NNRTIs among HIV-1-infected treatment-experienced and -naïve patients from Poland.

Methods: Resistance to DOR and other NNRTIs was assessed in two datasets: 1760 antiretroviral treatment-naïve HIV-1 patients and 200 treatment-experienced patients. Read More

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Cardiotoxicity of BTK inhibitors: ibrutinib and beyond.

Expert Rev Hematol 2022 04 22;15(4):321-331. Epub 2022 Apr 22.

Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical CenterHarold C. , Dallas, TX, USA.

Introduction: The development of Brutons Tyrosine Kinase (BTK) inhibitors has transformed the treatment of B-cell malignancies and other non-malignant conditions. Management of the unique cardiotoxic profile of these agents requires prompt recognition and a multi-disciplinary approach.

Areas Covered: The increasing indications and addition of newer agents to clinical practice and emergence of BTK inhibitor-related cardiac adverse events have complicated the management decisions for utilization of this class of therapy. Read More

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Immunogenicity of the mRNA-1273 COVID-19 vaccine in adult patients with inborn errors of immunity.

J Allergy Clin Immunol 2022 Jun 11;149(6):1949-1957. Epub 2022 Apr 11.

Department of Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Background: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore of great importance in this group, but little is known about the immunogenicity of COVID-19 vaccines in these patients.

Objectives: We sought to study humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult patients with IEI. Read More

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Keratoconjunctivitis as a Single Entity in X-linked Agammaglobulinemia?

Ocul Immunol Inflamm 2022 Apr 11:1-6. Epub 2022 Apr 11.

Department of Ophthalmology, University Medical Center, Greifswald, Germany.

Purpose: To report a case of a male patient with a severe corneal and conjunctival immunopathy likely caused by an X-linked agammaglobulinemia.

Methods: A clinical case report with observation results from 2001-2021.

Results: A severe corneal immunopathy of both eyes is reported in a retrospective long-term observation of nearly twenty years in a 32-year-old male patient with X-linked agammaglobulinemia (XLA). Read More

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Zanubrutinib for the treatment of adults with Waldenstrom macroglobulinemia.

Expert Rev Anticancer Ther 2022 May 22;22(5):471-478. Epub 2022 Apr 22.

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA.

Introduction: The development of Bruton tyrosine kinase (BTK) inhibitors has significantly changed the treatment landscape for patients with Waldenström macroglobulinemia (WM). Ibrutinib was the first BTK inhibitor to receive FDA approval for this disease, but in recent years additional more selective BTK inhibitors have become available. Zanubrutinib, the most recently FDA-approved therapy for WM, has demonstrated comparable efficacy regarding hematologic response, but with an improved side effect profile compared to other BTK inhibitors. Read More

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Improved HUMARA for the Detection of X-Linked Agammaglobulinemia Carriers.

Genet Test Mol Biomarkers 2022 Apr 8;26(4):220-227. Epub 2022 Apr 8.

Laboratorio de Inmunodeficiencias, Instituto Nacional de Pediatría, Ciudad de México, México.

Fragment analysis of exon 1 of the human androgen receptor, known as HUMARA, is a polymerase chain reaction (PCR)-based method for detecting X-linked agammaglobulinemia (XLA) carriers. This method takes advantage of X-chromosome inactivation (XCI) in female cells. XLA is caused by mutations in the Bruton tyrosine kinase () gene, located in Xq22. Read More

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Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report.

BMC Pediatr 2022 04 5;22(1):181. Epub 2022 Apr 5.

Bioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTIC, Av. Getulio Vargas, 333, Quitandinha CEP: 25651-075 Petrópolis, Rio de Janeiro, Brazil.

Background: X-linked agammaglobulinemia (XLA) is an Inborn Errors of Immunity (IEI) characterized by pan-hypogammaglobulinemia and low numbers of B lymphocytes due to mutations in BTK gene. Usually, XLA patients are not susceptible to respiratory tract infections by viruses and do not present interstitial lung disease (ILD) such as bronchiolitis obliterans (BO) as a consequence of acute or chronic bacterial infections of the respiratory tract. Although many pathogenic variants have already been described in XLA, the heterogeneous clinical presentations in affected patients suggest a more complex genetic landscape underlying this disorder. Read More

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Campylobacter infection in 4 patients treated with ibrutinib.

Eur J Clin Microbiol Infect Dis 2022 May 18;41(5):849-852. Epub 2022 Mar 18.

Clinical Immunology Department, Hôpital Saint Louis, Paris, France.

Ibrutinib is a Bruton tyrosine kinase (BTK) inhibitor used in B-cell lymphoproliferative disorders. Patients with genetic BTK deficiency are susceptible to recurrent and severe Campylobacter infections. We report 4 patients treated with ibrutinib who developed chronic or extra-digestive campylobacteriosis resembling ibrutinib-related adverse events including diarrhea (n = 4), panniculitis (n = 2), and arthritis (n = 1). Read More

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Dual BTK/SYK inhibition with CG-806 (luxeptinib) disrupts B-cell receptor and Bcl-2 signaling networks in mantle cell lymphoma.

Cell Death Dis 2022 Mar 16;13(3):246. Epub 2022 Mar 16.

City of Hope National Medical Center, Duarte, CA, USA.

Aberrant B-cell receptor (BCR) signaling is a key driver in lymphoid malignancies. Bruton tyrosine kinase (BTK) inhibitors that disrupt BCR signaling have received regulatory approvals in therapy of mantle cell lymphoma (MCL). However, responses are incomplete and patients who experience BTK inhibitor therapy failure have dire outcomes. Read More

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X-Linked Agammaglobulinemia: Infection Frequency and Infection-Related Mortality in the USIDNET Registry.

J Clin Immunol 2022 May 15;42(4):827-836. Epub 2022 Mar 15.

Weill Cornell Medicine, New York, NY, USA.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to B lymphocyte deficiency and susceptibility to infection. A potential benefit of earlier diagnosis and treatment initiation on morbidity and mortality in XLA is incompletely understood. In the USIDNET Registry, we describe infection frequency and infection-related mortality in patients with XLA and their relationship to age of diagnosis and treatment initiation. Read More

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Health-Related Quality of Life in 91 Patients with X-Linked Agammaglobulinemia.

J Clin Immunol 2022 May 14;42(4):811-818. Epub 2022 Mar 14.

Division of Immunology, Department of Pediatrics, University of Washington, Seattle, WA, 98101, USA.

Purpose: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency (PID) caused by a defect in the gene encoding for Bruton tyrosine kinase (BTK). In the absence of a functional BTK, patients have low or absent circulating B cells and low or absent serum immunoglobulin. Despite gammaglobulin replacement and prompt use of antimicrobial agents, patients with XLA continue to experience infectious and non-infectious complications throughout their lifetime. Read More

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Mantle cell lymphoma in 2022-A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments.

Am J Hematol 2022 05;97(5):638-656

Department of Lymphoma/Myeloma. Mantle cell lymphoma center of excellence, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

The field of mantle cell lymphoma (MCL) has witnessed remarkable progress due to relentless advances in molecular pathogenesis, prognostication, and newer treatments. MCL consists of a spectrum of clinical subtypes. Rarely, atypical cyclin D1-negative MCL and in situ MCL neoplasia are identified. Read More

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Recent development of BTK-based dual inhibitors in the treatment of cancers.

Eur J Med Chem 2022 Apr 25;233:114232. Epub 2022 Feb 25.

School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China. Electronic address:

Bruton's tyrosine kinase (BTK) is a promising target in the treatment of various cancers. Despite the early success of BTK inhibitors in the clinic, these single-target drug therapies have limitations in their clinical applications, such as drug resistance. Several alternative strategies have been developed, including the use of dual inhibitors, to maximize the therapeutic potential of anticancer drugs. Read More

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Identification of four novel mutations in BTK from six Chinese families with X-linked agammaglobulinemia.

Clin Chim Acta 2022 Jun 1;531:48-55. Epub 2022 Mar 1.

Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, China; Laboratory of Molecular Genetics, Hunan Jiahui Genetics Hospital, Changsha, Hunan, China. Electronic address:

Background: The defect of Bruton's tyrosine kinase (BTK) gene resulted in X-linked agammaglobulinemia (XLA), which is characterized by recurrent bacterial infections, immunodeficiency with low B-cell numbers and immunoglobulin. Diagnosis of XLA depends on clinical phenotype and genetic testing.

Methods: Six unrelated Chinese families with high suspicion of XLA were enrolled in this study. Read More

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Infections With Enterohepatic Non- Species in X-Linked Agammaglobulinemia: Clinical Cases and Review of the Literature.

Front Cell Infect Microbiol 2021 4;11:807136. Epub 2022 Feb 4.

Immunodeficiency Research Unit, National Institute of Pediatrics, Mexico City, Mexico.

The genus is classified into two main groups according to its habitat: gastric and enterohepatic. Patients with X-linked agammaglobulinemia (XLA) appear to be associated with invasive infection with enterohepatic non-Helicobacter pylori species (NHPH), mainly and . Such infections are difficult to control and have a high potential for recurrence. Read More

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Retrospective study of 98 patients with X-linked agammaglobulinemia complicated with arthritis.

Clin Rheumatol 2022 Jun 16;41(6):1889-1897. Epub 2022 Feb 16.

Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, 400015, China.

Objective: We preformed this retrospective study of clinical manifestation, imaging feature, and mutations to describe joint involvement in X-linked agammaglobulinemia (XLA) patients, aimed to provide recommendation for physicians.

Methods: A total number of 98 XLA patients who have been diagnosed between January 2000 and February 2020 were enrolled and grouped based on whether they developed arthritis and analyzed for the clinical, imaging, and gene mutation data using the t test or the Mann-Whitney test.

Results: Forty-five out of 98 patients (45. Read More

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Clinical and laboratory observation on immunoglobulin replacement therapy switching from an intravenous to a subcutaneous route in a Malaysian X-linked agammaglobulinemia patient.

Med J Malaysia 2022 Jan;77(1):95-97

7Tunku Azizah Hospital for Women & Children, Kuala Lumpur, Malaysia.

We report a clinical and laboratory observation in a boy with X-linked agammaglobulinemia (XLA) who underwent an immunoglobulin replacement therapy (IRT) via the subcutaneous route (IGSC) seven years after his IRT via intravenous route (IGIV). He was free of invasive infections when on IGIV but not the troublesome coughs a week before the next infusion. A switch to a subcutaneous route resulted in significant improvement of symptoms with good weight gain. Read More

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January 2022

Clinical, immunological and genomic characteristics of children with X-linked agammaglobulinemia from Kerala, South India.

Hum Immunol 2022 Apr 21;83(4):335-345. Epub 2022 Jan 21.

CSIR-Institute of Genomics and Integrative Biology, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India. Electronic address:

X-linked agammaglobulinemia (XLA) is an X-linked recessive primary immunodeficiency disorder caused due to a pathogenic variant in the Bruton tyrosine (BTK) gene with an incidence of 1:379,000 live births and 1:190,000 male births. Patients affected with XLA present with recurrent infections of the gastrointestinal and respiratory tracts. Here we report the first case series of 17 XLA patients of 10 South Indian families with a wide spectrum of clinical and genetic features. Read More

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X-Linked Agammaglobulinemia with Kawasaki Disease.

Indian J Pediatr 2022 Apr 11;89(4):413. Epub 2022 Jan 11.

Department of Pediatrics, Lady Hardinge Medical College and assosciated Kalawati Saran Children Hospital, New Delhi, 110001, India.

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Inhibition of Bruton Tyrosine Kinase Reduces Neuroimmune Cascade and Promotes Recovery after Spinal Cord Injury.

Int J Mol Sci 2021 Dec 29;23(1). Epub 2021 Dec 29.

Spinal Cord and Brain Injury Research Center, Department of Neuroscience, College of Medicine, University of Kentucky, 741 S. Limestone Street, Lexington, KY 40536, USA.

Microglia/astrocyte and B cell neuroimmune responses are major contributors to the neurological deficits after traumatic spinal cord injury (SCI). Bruton tyrosine kinase (BTK) activation mechanistically links these neuroimmune mechanisms. Our objective is to use Ibrutinib, an FDA-approved BTK inhibitor, to inhibit the neuroimmune cascade thereby improving locomotor recovery after SCI. Read More

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December 2021

B cell repertoire in patients with a novel BTK mutation: expanding the spectrum of atypical X-linked agammaglobulinemia.

Immunol Res 2022 04 10;70(2):216-223. Epub 2022 Jan 10.

Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

X-linked agammaglobulinemia (XLA) is caused by mutations in the Bruton tyrosine kinase) BTK) gene. Affected patients have severely reduced amounts of circulating B cells. Patients with atypical XLA may have residual circulating B cells, and there are few studies exploring these cells' repertoire. Read More

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Current Treatment of Chronic Lymphocytic Leukemia: The Diminishing Role of Chemoimmunotherapy.

Drugs 2022 Feb 21;82(2):133-143. Epub 2021 Dec 21.

Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10021, USA.

In this review, we examine the literature supporting treatment decision making in the front-line and relapsed/refractory settings for patients with chronic lymphocytic leukemia (CLL). In the front-line setting, novel-agent-based approaches, including continuous Bruton tyrosine kinase (BTK) inhibitor-based therapy and time-limited venetoclax with obinutuzumab, have demonstrated survival benefit over chemoimmunotherapy. While novel-agent-based front-line approaches are appropriate for most patients, fludarabine, cyclophosphamide, and rituximab (FCR) remains a consideration for a selected population of young patients with immunoglobulin heavy chain variable region gene (IGHV)-mutated disease because of the possibility of a prolonged remission following FCR. Read More

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February 2022

Pulmonary Radiological Manifestations of Humoral and Combined Immunodeficiencies in a Tertiary Pediatric Center.

Iran J Allergy Asthma Immunol 2021 Dec 8;20(6):693-699. Epub 2021 Dec 8.

Pediatric Infections Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Respiratory diseases are considered as significant causes of morbidity and mortality in primary immunodeficiencies. This study aimed to reveal the radiologic patterns of thoracic involvement in these disorders. A total of 58 patients, including 38 cases with combined cellular-humoral and 20 cases with humoral immunodeficiencies, were enrolled in this study. Read More

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December 2021

Bruton Tyrosine Kinase Inhibitors in B-Cell Malignancies: Their Use and Differential Features.

Authors:
Matt Shirley

Target Oncol 2022 01 14;17(1):69-84. Epub 2021 Dec 14.

Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

Starting with the first-in-class agent ibrutinib, the development of Bruton tyrosine kinase (BTK) inhibitors has led to dramatic improvements in the management of B-cell malignancies. Subsequently, more-highly selective second-generation BTK inhibitors (including acalabrutinib, zanubrutinib, tirabrutinib and orelabrutinib) have been developed, primarily with an aim to reduce off-target toxicities. More recently, third-generation agents including the non-covalent BTK inhibitors pirtobrutinib and nemtabrutinib have entered later-stage clinical development. Read More

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January 2022

BTK-inhibitor drug covalent binding to lysine in human serum albumin using LC-MS/MS.

Drug Metab Pharmacokinet 2022 Feb 12;42:100433. Epub 2021 Nov 12.

Biogen, DMPK, 225 Binney St, Cambridge, MA, 02142, United States. Electronic address:

Irreversible Bruton's tyrosine kinase (BTK) inhibitor drugs are designed to bind covalently to a free-thiol cysteine in the BTK protein active site. However, these reactive drugs bind to off-target proteins as well. In this study, seven BTK-inhibitor drugs containing acrylamide warheads were incubated with human serum albumin (HSA) and analyzed using an LC-MS/MS peptide mapping approach to determine the amino acid sites of drug covalent binding. Read More

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February 2022

Structure-based virtual screening and biological evaluation of novel small-molecule BTK inhibitors.

J Enzyme Inhib Med Chem 2022 Dec;37(1):226-235

Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.

Bruton tyrosine kinase (BTK) is linked to multiple signalling pathways that regulate cellular survival, activation, and proliferation. A covalent BTK inhibitor has shown favourable outcomes for treating B cell malignant leukaemia. However, covalent inhibitors require a high reactive warhead that may contribute to unexpected toxicity, poor selectivity, or reduced effectiveness in solid tumours. Read More

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December 2022