Ibrutinib blocks Btk-dependent NF-ĸB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis

Amelia Bercusson; Thomas Colley; Anand Shah; Adilia Warris; Darius Armstrong-James

doi:10.1182/blood-2017-12-823393

Ibrutinib blocks Btk-dependent NF-ĸB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis

Amelia Bercusson
, Thomas Colley
, Anand Shah
, Adilia Warris
, Darius Armstrong-James

Applied Medicine

Research output: Contribution to journal › Article › peer-review

109 Citations (Scopus)

11 Downloads (Pure)

Abstract

Ibrutinib is a small molecule Bruton tyrosine kinase (Btk) inhibitor approved by the Food and Drug Administration for clinical use in the treatment of chronic lymphocytic leukemia, Waldenström macroglobulinemia, and as a second-line treatment of lymphoma and chronic graft-versus-host disease.1 An association with pulmonary aspergillosis was observed shortly after Ibrutinib was licensed for use.2 A recent phase Ib study of Ibrutinib treatment of primary central nervous system lymphoma reported a 39% incidence of invasive aspergillosis, in patients concurrently treated with corticosteroids, in the absence of neutropenia.3 Studies of Aspergillus fumigatus infection in Btk−/− mice revealed focal pneumonia and large airway mucous plugs, mirroring findings in macrophage-depleted models of pulmonary aspergillosis.

Original language	English
Pages (from-to)	1985-1988
Number of pages	4
Journal	Blood
Volume	132
Issue number	18
Early online date	18 Jul 2018
DOIs	https://doi.org/10.1182/blood-2017-12-823393
Publication status	Published - 1 Nov 2018

Bibliographical note

AB and AW are supported by the Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (G097377). AS was funded by an MRC Clinical Research Fellowship (MR/K002708/1). AW is supported by the MRC Centre for Medical Mycology (MR/N006364/1) at the University of Aberdeen. DAJ is supported by a Wellcome Trust Seed Award (204566/Z/16/Z).

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Ibrutinib blocks Btk-dependent NF-ĸB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosisFinal published version, 976 KBLicence: Other

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title = "Ibrutinib blocks Btk-dependent NF-ĸB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis",

abstract = "Ibrutinib is a small molecule Bruton tyrosine kinase (Btk) inhibitor approved by the Food and Drug Administration for clinical use in the treatment of chronic lymphocytic leukemia, Waldenstr{\"o}m macroglobulinemia, and as a second-line treatment of lymphoma and chronic graft-versus-host disease.1 An association with pulmonary aspergillosis was observed shortly after Ibrutinib was licensed for use.2 A recent phase Ib study of Ibrutinib treatment of primary central nervous system lymphoma reported a 39\% incidence of invasive aspergillosis, in patients concurrently treated with corticosteroids, in the absence of neutropenia.3 Studies of Aspergillus fumigatus infection in Btk−/− mice revealed focal pneumonia and large airway mucous plugs, mirroring findings in macrophage-depleted models of pulmonary aspergillosis.",

author = "Amelia Bercusson and Thomas Colley and Anand Shah and Adilia Warris and Darius Armstrong-James",

note = "AB and AW are supported by the Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (G097377). AS was funded by an MRC Clinical Research Fellowship (MR/K002708/1). AW is supported by the MRC Centre for Medical Mycology (MR/N006364/1) at the University of Aberdeen. DAJ is supported by a Wellcome Trust Seed Award (204566/Z/16/Z).",

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doi = "10.1182/blood-2017-12-823393",

language = "English",

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T1 - Ibrutinib blocks Btk-dependent NF-ĸB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis

AU - Bercusson, Amelia

AU - Colley, Thomas

AU - Shah, Anand

AU - Warris, Adilia

AU - Armstrong-James, Darius

N1 - AB and AW are supported by the Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (G097377). AS was funded by an MRC Clinical Research Fellowship (MR/K002708/1). AW is supported by the MRC Centre for Medical Mycology (MR/N006364/1) at the University of Aberdeen. DAJ is supported by a Wellcome Trust Seed Award (204566/Z/16/Z).

PY - 2018/11/1

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N2 - Ibrutinib is a small molecule Bruton tyrosine kinase (Btk) inhibitor approved by the Food and Drug Administration for clinical use in the treatment of chronic lymphocytic leukemia, Waldenström macroglobulinemia, and as a second-line treatment of lymphoma and chronic graft-versus-host disease.1 An association with pulmonary aspergillosis was observed shortly after Ibrutinib was licensed for use.2 A recent phase Ib study of Ibrutinib treatment of primary central nervous system lymphoma reported a 39% incidence of invasive aspergillosis, in patients concurrently treated with corticosteroids, in the absence of neutropenia.3 Studies of Aspergillus fumigatus infection in Btk−/− mice revealed focal pneumonia and large airway mucous plugs, mirroring findings in macrophage-depleted models of pulmonary aspergillosis.

AB - Ibrutinib is a small molecule Bruton tyrosine kinase (Btk) inhibitor approved by the Food and Drug Administration for clinical use in the treatment of chronic lymphocytic leukemia, Waldenström macroglobulinemia, and as a second-line treatment of lymphoma and chronic graft-versus-host disease.1 An association with pulmonary aspergillosis was observed shortly after Ibrutinib was licensed for use.2 A recent phase Ib study of Ibrutinib treatment of primary central nervous system lymphoma reported a 39% incidence of invasive aspergillosis, in patients concurrently treated with corticosteroids, in the absence of neutropenia.3 Studies of Aspergillus fumigatus infection in Btk−/− mice revealed focal pneumonia and large airway mucous plugs, mirroring findings in macrophage-depleted models of pulmonary aspergillosis.

U2 - 10.1182/blood-2017-12-823393

DO - 10.1182/blood-2017-12-823393

M3 - Article

SN - 0006-4971

VL - 132

SP - 1985

EP - 1988

JO - Blood

JF - Blood

IS - 18

ER -

Ibrutinib blocks Btk-dependent NF-ĸB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis

Abstract

Bibliographical note

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