Inhibition of Bruton tyrosine kinase in patients with severe COVID-19.

Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors Aged Aged, 80 and over Benzamides / pharmacology Betacoronavirus COVID-19 Coronavirus Infections / drug therapy Critical Illness Female Follow-Up Studies Humans Inflammation / drug therapy Interleukin-6 / metabolism Male Middle Aged Monocytes / metabolism Pandemics Pneumonia, Viral / drug therapy Prospective Studies Pyrazines / pharmacology Respiration, Artificial SARS-CoV-2 Treatment Outcome COVID-19 Drug Treatment

Journal

Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624

Informations de publication

Date de publication:
05 06 2020
Historique:
received: 26 05 2020
accepted: 03 06 2020
entrez: 7 6 2020
pubmed: 7 6 2020
medline: 20 6 2020
Statut: ppublish

Résumé

Patients with severe COVID-19 have a hyperinflammatory immune response suggestive of macrophage activation. Bruton tyrosine kinase (BTK) regulates macrophage signaling and activation. Acalabrutinib, a selective BTK inhibitor, was administered off-label to 19 patients hospitalized with severe COVID-19 (11 on supplemental oxygen; 8 on mechanical ventilation), 18 of whom had increasing oxygen requirements at baseline. Over a 10-14 day treatment course, acalabrutinib improved oxygenation in a majority of patients, often within 1-3 days, and had no discernable toxicity. Measures of inflammation - C-reactive protein and IL-6 - normalized quickly in most patients, as did lymphopenia, in correlation with improved oxygenation. At the end of acalabrutinib treatment, 8/11 (72.7%) patients in the supplemental oxygen cohort had been discharged on room air, and 4/8 (50%) patients in the mechanical ventilation cohort had been successfully extubated, with 2/8 (25%) discharged on room air. Ex vivo analysis revealed significantly elevated BTK activity, as evidenced by autophosphorylation, and increased IL-6 production in blood monocytes from patients with severe COVID-19 compared with blood monocytes from healthy volunteers. These results suggest that targeting excessive host inflammation with a BTK inhibitor is a therapeutic strategy in severe COVID-19 and has led to a confirmatory international prospective randomized controlled clinical trial.

Identifiants

DOI: 10.1126/sciimmunol.abd0110 PMID: 32503877 PMC: PMC7274761
pubmed: 32503877
pii: 5/48/eabd0110
doi: 10.1126/sciimmunol.abd0110
pmc: PMC7274761
pii:
doi:

Substances chimiques

Benzamides 0
IL6 protein, human 0
Interleukin-6 0
Pyrazines 0
Agammaglobulinaemia Tyrosine Kinase EC 2.7.10.2
BTK protein, human EC 2.7.10.2
acalabrutinib I42748ELQW

Types de publication

Journal Article Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2020, American Association for the Advancement of Science.

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Auteurs

Mark Roschewski (M)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.
ORCID: 0000-0003-0278-2635

Michail S Lionakis (MS)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.

Jeff P Sharman (JP)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.

Joseph Roswarski (J)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.

Andre Goy (A)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.

M Andrew Monticelli (MA)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.

Michael Roshon (M)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.
ORCID: 0000-0002-8929-5583

Stephen H Wrzesinski (SH)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.
ORCID: 0000-0002-0133-8172

Jigar V Desai (JV)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.
ORCID: 0000-0002-8823-0796

Marissa A Zarakas (MA)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.

Jacob Collen (J)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.

Keith Rose (K)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.

Ahmed Hamdy (A)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.

Raquel Izumi (R)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.

George W Wright (GW)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.
ORCID: 0000-0003-0003-0843

Kevin K Chung (KK)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.
ORCID: 0000-0002-2781-3787

Jose Baselga (J)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.
ORCID: 0000-0003-1361-4063

Louis M Staudt (LM)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD.
ORCID: 0000-0002-1735-2892

Wyndham H Wilson (WH)

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO; US Acute Care Solutions, Canton, OH; Department of Medicine, St. Peter's Hospital and US Oncology, Albany, NY; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Acerta Pharma, South San Francisco, CA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA AstraZeneca, One MedImmune Way, Gaithersburg, MD wilsonw@mail.nih.gov.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-tyrosine kinases › Agammaglobulinaemia tyrosine kinase › Inhibition of Bruton tyrosine kinase in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Inhibition of Bruton tyrosine kinase in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Inhibition of Bruton tyrosine kinase in...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Benzoates › Benzamides › Inhibition of Bruton tyrosine kinase in...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Inhibition of Bruton tyrosine kinase in...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Inhibition of Bruton tyrosine kinase in...
questionsmedicales.fr › Infection › Maladies virales › Infections à virus à ARN › Infections à Nidovirales › Infections à Coronaviridae › Infections à coronavirus › Inhibition of Bruton tyrosine kinase in...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie grave › Inhibition of Bruton tyrosine kinase in...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études de suivi › Inhibition of Bruton tyrosine kinase in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Inhibition of Bruton tyrosine kinase in...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Inhibition of Bruton tyrosine kinase in...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-6 › Inhibition of Bruton tyrosine kinase in...
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