Activation of natural killer cells by rituximab in granulomatosis with polyangiitis

In the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we investigated whether natural killer (NK) cells may play a role in rituximab's mechanism of action in GPA. B cell depletion, NK cell degranulation,...

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Published inArthritis research & therapy Vol. 21; no. 1; p. 277
Main Authors Urlaub, Doris, Zhao, Shuyang, Blank, Norbert, Bergner, Raoul, Claus, Maren, Tretter, Theresa, Lorenz, Hanns-Martin, Watzl, Carsten, Merkt, Wolfgang
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LanguageEnglish
Published England BioMed Central Ltd 11.12.2019
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Abstract In the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we investigated whether natural killer (NK) cells may play a role in rituximab's mechanism of action in GPA. B cell depletion, NK cell degranulation, and the expression of CD69 and CD16 on NK cells were measured in a series of in vitro experiments using peripheral blood mononuclear cells (PBMCs). In vivo activation of NK cells was investigated in patients receiving rituximab infusions. Cells were analyzed by seven-color flow cytometry. NK cells from GPA patients were activated by immobilized rituximab. Also soluble rituximab activated NK cells, provided that B cells were present. NK cells degranulated and expressed the activation marker CD69 while CD16 expression was decreased. This activation of NK cells by soluble rituximab was accompanied by a reduction of B cells. The next-generation anti-CD20 antibody obinutuzumab showed stronger effects compared to rituximab on both the reduction of B cells and the activation of NK cells. Finally, we found that rituximab led to the activation of NK cells in vivo, provided that B cells were not depleted due to prior rituximab infusions. B cell-bound rituximab activates NK cells in GPA. While NK cells therefore participate in rituximab's mechanism of action in humans, their potential may be more efficiently exploited, e.g., by Fc engineering of therapeutic antibodies.
AbstractList OBJECTIVEIn the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we investigated whether natural killer (NK) cells may play a role in rituximab's mechanism of action in GPA. METHODSB cell depletion, NK cell degranulation, and the expression of CD69 and CD16 on NK cells were measured in a series of in vitro experiments using peripheral blood mononuclear cells (PBMCs). In vivo activation of NK cells was investigated in patients receiving rituximab infusions. Cells were analyzed by seven-color flow cytometry. RESULTSNK cells from GPA patients were activated by immobilized rituximab. Also soluble rituximab activated NK cells, provided that B cells were present. NK cells degranulated and expressed the activation marker CD69 while CD16 expression was decreased. This activation of NK cells by soluble rituximab was accompanied by a reduction of B cells. The next-generation anti-CD20 antibody obinutuzumab showed stronger effects compared to rituximab on both the reduction of B cells and the activation of NK cells. Finally, we found that rituximab led to the activation of NK cells in vivo, provided that B cells were not depleted due to prior rituximab infusions. CONCLUSIONB cell-bound rituximab activates NK cells in GPA. While NK cells therefore participate in rituximab's mechanism of action in humans, their potential may be more efficiently exploited, e.g., by Fc engineering of therapeutic antibodies.
Objective In the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we investigated whether natural killer (NK) cells may play a role in rituximab's mechanism of action in GPA. Methods B cell depletion, NK cell degranulation, and the expression of CD69 and CD16 on NK cells were measured in a series of in vitro experiments using peripheral blood mononuclear cells (PBMCs). In vivo activation of NK cells was investigated in patients receiving rituximab infusions. Cells were analyzed by seven-color flow cytometry. Results NK cells from GPA patients were activated by immobilized rituximab. Also soluble rituximab activated NK cells, provided that B cells were present. NK cells degranulated and expressed the activation marker CD69 while CD16 expression was decreased. This activation of NK cells by soluble rituximab was accompanied by a reduction of B cells. The next-generation anti-CD20 antibody obinutuzumab showed stronger effects compared to rituximab on both the reduction of B cells and the activation of NK cells. Finally, we found that rituximab led to the activation of NK cells in vivo, provided that B cells were not depleted due to prior rituximab infusions. Conclusion B cell-bound rituximab activates NK cells in GPA. While NK cells therefore participate in rituximab's mechanism of action in humans, their potential may be more efficiently exploited, e.g., by Fc engineering of therapeutic antibodies. Keywords: Natural killer cells, Rituximab, B cell depletion, Rheumatic diseases, ANCA-associated vasculitis, Granulomatosis with polyangiitis, Obinutuzumab, Antibody-dependent cellular cytotoxicity (ADCC), Fc-[gamma]-receptor IIIa (Fc[gamma]RIIIa; CD16)
In the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we investigated whether natural killer (NK) cells may play a role in rituximab's mechanism of action in GPA. B cell depletion, NK cell degranulation, and the expression of CD69 and CD16 on NK cells were measured in a series of in vitro experiments using peripheral blood mononuclear cells (PBMCs). In vivo activation of NK cells was investigated in patients receiving rituximab infusions. Cells were analyzed by seven-color flow cytometry. NK cells from GPA patients were activated by immobilized rituximab. Also soluble rituximab activated NK cells, provided that B cells were present. NK cells degranulated and expressed the activation marker CD69 while CD16 expression was decreased. This activation of NK cells by soluble rituximab was accompanied by a reduction of B cells. The next-generation anti-CD20 antibody obinutuzumab showed stronger effects compared to rituximab on both the reduction of B cells and the activation of NK cells. Finally, we found that rituximab led to the activation of NK cells in vivo, provided that B cells were not depleted due to prior rituximab infusions. B cell-bound rituximab activates NK cells in GPA. While NK cells therefore participate in rituximab's mechanism of action in humans, their potential may be more efficiently exploited, e.g., by Fc engineering of therapeutic antibodies.
Abstract Objective In the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we investigated whether natural killer (NK) cells may play a role in rituximab’s mechanism of action in GPA. Methods B cell depletion, NK cell degranulation, and the expression of CD69 and CD16 on NK cells were measured in a series of in vitro experiments using peripheral blood mononuclear cells (PBMCs). In vivo activation of NK cells was investigated in patients receiving rituximab infusions. Cells were analyzed by seven-color flow cytometry. Results NK cells from GPA patients were activated by immobilized rituximab. Also soluble rituximab activated NK cells, provided that B cells were present. NK cells degranulated and expressed the activation marker CD69 while CD16 expression was decreased. This activation of NK cells by soluble rituximab was accompanied by a reduction of B cells. The next-generation anti-CD20 antibody obinutuzumab showed stronger effects compared to rituximab on both the reduction of B cells and the activation of NK cells. Finally, we found that rituximab led to the activation of NK cells in vivo, provided that B cells were not depleted due to prior rituximab infusions. Conclusion B cell-bound rituximab activates NK cells in GPA. While NK cells therefore participate in rituximab’s mechanism of action in humans, their potential may be more efficiently exploited, e.g., by Fc engineering of therapeutic antibodies.
Objective In the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we investigated whether natural killer (NK) cells may play a role in rituximab’s mechanism of action in GPA. Methods B cell depletion, NK cell degranulation, and the expression of CD69 and CD16 on NK cells were measured in a series of in vitro experiments using peripheral blood mononuclear cells (PBMCs). In vivo activation of NK cells was investigated in patients receiving rituximab infusions. Cells were analyzed by seven-color flow cytometry. Results NK cells from GPA patients were activated by immobilized rituximab. Also soluble rituximab activated NK cells, provided that B cells were present. NK cells degranulated and expressed the activation marker CD69 while CD16 expression was decreased. This activation of NK cells by soluble rituximab was accompanied by a reduction of B cells. The next-generation anti-CD20 antibody obinutuzumab showed stronger effects compared to rituximab on both the reduction of B cells and the activation of NK cells. Finally, we found that rituximab led to the activation of NK cells in vivo, provided that B cells were not depleted due to prior rituximab infusions. Conclusion B cell-bound rituximab activates NK cells in GPA. While NK cells therefore participate in rituximab’s mechanism of action in humans, their potential may be more efficiently exploited, e.g., by Fc engineering of therapeutic antibodies.
In the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we investigated whether natural killer (NK) cells may play a role in rituximab's mechanism of action in GPA. B cell depletion, NK cell degranulation, and the expression of CD69 and CD16 on NK cells were measured in a series of in vitro experiments using peripheral blood mononuclear cells (PBMCs). In vivo activation of NK cells was investigated in patients receiving rituximab infusions. Cells were analyzed by seven-color flow cytometry. NK cells from GPA patients were activated by immobilized rituximab. Also soluble rituximab activated NK cells, provided that B cells were present. NK cells degranulated and expressed the activation marker CD69 while CD16 expression was decreased. This activation of NK cells by soluble rituximab was accompanied by a reduction of B cells. The next-generation anti-CD20 antibody obinutuzumab showed stronger effects compared to rituximab on both the reduction of B cells and the activation of NK cells. Finally, we found that rituximab led to the activation of NK cells in vivo, provided that B cells were not depleted due to prior rituximab infusions. B cell-bound rituximab activates NK cells in GPA. While NK cells therefore participate in rituximab's mechanism of action in humans, their potential may be more efficiently exploited, e.g., by Fc engineering of therapeutic antibodies.
ArticleNumber 277
Audience Academic
Author Bergner, Raoul
Merkt, Wolfgang
Blank, Norbert
Watzl, Carsten
Tretter, Theresa
Urlaub, Doris
Zhao, Shuyang
Claus, Maren
Lorenz, Hanns-Martin
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Cites_doi 10.1200/JCO.2005.06.059
10.4049/jimmunol.1202065
10.1182/blood-2013-02-482570
10.1056/NEJMoa1213277
10.1136/annrheumdis-2017-212768
10.1182/blood-2005-04-1351
10.1002/art.37715
10.1038/cmi.2013.10
10.1056/NEJMoa1404231
10.1002/art.39822
10.1182/blood-2007-02-074716
10.1182/blood-2009-06-225979
10.1186/s13075-017-1306-0
10.1056/NEJMoa0909905
10.1016/j.it.2015.04.005
10.1002/art.10764
10.1007/s00296-014-3015-1
10.1182/blood-2009-01-200469
10.1182/blood.V99.3.754
10.1016/j.jim.2014.01.017
10.1053/j.seminhematol.2010.01.001
10.1186/s13075-016-1098-7
10.1186/s13075-016-1101-3
10.1182/blood-2017-08-752170
10.1200/JCO.2003.05.013
10.1136/annrheumdis-2011-200337
10.1073/pnas.1705301114
10.1016/j.jim.2004.08.008
10.1158/1078-0432.CCR-1087-3
10.1182/blood-2011-05-351411
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Issue 1
Keywords Obinutuzumab
Rheumatic diseases
Granulomatosis with polyangiitis
Rituximab
Fc-γ-receptor IIIa (FcγRIIIa; CD16)
B cell depletion
Natural killer cells
ANCA-associated vasculitis
Antibody-dependent cellular cytotoxicity (ADCC)
Language English
License Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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PublicationTitle Arthritis research & therapy
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References JC Jennette (2054_CR1) 2013; 65
U Specks (2054_CR4) 2013; 369
G Alter (2054_CR27) 2004; 294
R Cartin-Ceba (2054_CR22) 2017; 69
D Herndler-Brandstetter (2054_CR21) 2017; 114
E Mossner (2054_CR25) 2010; 115
WK Weng (2054_CR13) 2003; 21
J Deguine (2054_CR20) 2012; 189
B Chaigne (2054_CR7) 2016; 34
YT Bryceson (2054_CR18) 2006; 107
SY Wang (2054_CR31) 2009; 114
L Guillevin (2054_CR3) 2014; 371
F Nimmerjahn (2054_CR9) 2015; 36
M Cheng (2054_CR29) 2013; 10
W Merkt (2054_CR23) 2016; 18
SP Treon (2054_CR12) 2005; 23
SA Beers (2054_CR8) 2010; 47
JH Anolik (2054_CR17) 2003; 48
A Ruyssen-Witrand (2054_CR15) 2012; 71
YH Lee (2054_CR16) 2014; 34
B Terrier (2054_CR5) 2018; 77
S Veeramani (2054_CR14) 2011; 118
W Merkt (2054_CR24) 2016; 18
SY Wang (2054_CR30) 2008; 111
JH Stone (2054_CR2) 2010; 363
G Cartron (2054_CR10) 2002; 99
MM Mata (2054_CR26) 2014; 406
WL Gluck (2054_CR11) 2004; 10
S Cooley (2054_CR28) 2018; 131
J Thiel (2054_CR6) 2017; 19
D Rudnicka (2054_CR19) 2013; 121
References_xml – volume: 23
  start-page: 474
  issue: 3
  year: 2005
  ident: 2054_CR12
  publication-title: J Clin Oncol
  doi: 10.1200/JCO.2005.06.059
  contributor:
    fullname: SP Treon
– volume: 189
  start-page: 5493
  issue: 12
  year: 2012
  ident: 2054_CR20
  publication-title: J Immunol
  doi: 10.4049/jimmunol.1202065
  contributor:
    fullname: J Deguine
– volume: 121
  start-page: 4694
  issue: 23
  year: 2013
  ident: 2054_CR19
  publication-title: Blood
  doi: 10.1182/blood-2013-02-482570
  contributor:
    fullname: D Rudnicka
– volume: 369
  start-page: 417
  issue: 5
  year: 2013
  ident: 2054_CR4
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1213277
  contributor:
    fullname: U Specks
– volume: 77
  start-page: 1150
  issue: 8
  year: 2018
  ident: 2054_CR5
  publication-title: Ann Rheum Dis
  doi: 10.1136/annrheumdis-2017-212768
  contributor:
    fullname: B Terrier
– volume: 107
  start-page: 159
  issue: 1
  year: 2006
  ident: 2054_CR18
  publication-title: Blood
  doi: 10.1182/blood-2005-04-1351
  contributor:
    fullname: YT Bryceson
– volume: 65
  start-page: 1
  issue: 1
  year: 2013
  ident: 2054_CR1
  publication-title: Arthritis Rheum
  doi: 10.1002/art.37715
  contributor:
    fullname: JC Jennette
– volume: 10
  start-page: 230
  issue: 3
  year: 2013
  ident: 2054_CR29
  publication-title: Cell Mol Immunol
  doi: 10.1038/cmi.2013.10
  contributor:
    fullname: M Cheng
– volume: 371
  start-page: 1771
  issue: 19
  year: 2014
  ident: 2054_CR3
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1404231
  contributor:
    fullname: L Guillevin
– volume: 69
  start-page: 169
  issue: 1
  year: 2017
  ident: 2054_CR22
  publication-title: Arthritis Rheumatol
  doi: 10.1002/art.39822
  contributor:
    fullname: R Cartin-Ceba
– volume: 111
  start-page: 1456
  issue: 3
  year: 2008
  ident: 2054_CR30
  publication-title: Blood
  doi: 10.1182/blood-2007-02-074716
  contributor:
    fullname: SY Wang
– volume: 115
  start-page: 4393
  issue: 22
  year: 2010
  ident: 2054_CR25
  publication-title: Blood
  doi: 10.1182/blood-2009-06-225979
  contributor:
    fullname: E Mossner
– volume: 19
  start-page: 101
  issue: 1
  year: 2017
  ident: 2054_CR6
  publication-title: Arthritis Res Ther
  doi: 10.1186/s13075-017-1306-0
  contributor:
    fullname: J Thiel
– volume: 363
  start-page: 221
  issue: 3
  year: 2010
  ident: 2054_CR2
  publication-title: New Engl J Med
  doi: 10.1056/NEJMoa0909905
  contributor:
    fullname: JH Stone
– volume: 36
  start-page: 325
  issue: 6
  year: 2015
  ident: 2054_CR9
  publication-title: Trends Immunol
  doi: 10.1016/j.it.2015.04.005
  contributor:
    fullname: F Nimmerjahn
– volume: 48
  start-page: 455
  issue: 2
  year: 2003
  ident: 2054_CR17
  publication-title: Arthritis Rheum
  doi: 10.1002/art.10764
  contributor:
    fullname: JH Anolik
– volume: 34
  start-page: 1409
  issue: 10
  year: 2014
  ident: 2054_CR16
  publication-title: Rheumatol Int
  doi: 10.1007/s00296-014-3015-1
  contributor:
    fullname: YH Lee
– volume: 114
  start-page: 5322
  issue: 26
  year: 2009
  ident: 2054_CR31
  publication-title: Blood
  doi: 10.1182/blood-2009-01-200469
  contributor:
    fullname: SY Wang
– volume: 99
  start-page: 754
  issue: 3
  year: 2002
  ident: 2054_CR10
  publication-title: Blood
  doi: 10.1182/blood.V99.3.754
  contributor:
    fullname: G Cartron
– volume: 406
  start-page: 1
  year: 2014
  ident: 2054_CR26
  publication-title: J Immunol Methods
  doi: 10.1016/j.jim.2014.01.017
  contributor:
    fullname: MM Mata
– volume: 34
  start-page: S121
  issue: 3 Suppl 97
  year: 2016
  ident: 2054_CR7
  publication-title: Clin Exp Rheumatol
  contributor:
    fullname: B Chaigne
– volume: 47
  start-page: 107
  issue: 2
  year: 2010
  ident: 2054_CR8
  publication-title: Semin Hematol
  doi: 10.1053/j.seminhematol.2010.01.001
  contributor:
    fullname: SA Beers
– volume: 18
  start-page: 204
  issue: 1
  year: 2016
  ident: 2054_CR23
  publication-title: Arthritis Res Ther
  doi: 10.1186/s13075-016-1098-7
  contributor:
    fullname: W Merkt
– volume: 18
  start-page: 206
  issue: 1
  year: 2016
  ident: 2054_CR24
  publication-title: Arthritis Res Ther
  doi: 10.1186/s13075-016-1101-3
  contributor:
    fullname: W Merkt
– volume: 131
  start-page: 1053
  issue: 10
  year: 2018
  ident: 2054_CR28
  publication-title: Blood
  doi: 10.1182/blood-2017-08-752170
  contributor:
    fullname: S Cooley
– volume: 21
  start-page: 3940
  issue: 21
  year: 2003
  ident: 2054_CR13
  publication-title: J Clin Oncol
  doi: 10.1200/JCO.2003.05.013
  contributor:
    fullname: WK Weng
– volume: 71
  start-page: 875
  issue: 6
  year: 2012
  ident: 2054_CR15
  publication-title: Ann Rheum Dis
  doi: 10.1136/annrheumdis-2011-200337
  contributor:
    fullname: A Ruyssen-Witrand
– volume: 114
  start-page: E9626
  issue: 45
  year: 2017
  ident: 2054_CR21
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1705301114
  contributor:
    fullname: D Herndler-Brandstetter
– volume: 294
  start-page: 15
  issue: 1–2
  year: 2004
  ident: 2054_CR27
  publication-title: J Immunol Methods
  doi: 10.1016/j.jim.2004.08.008
  contributor:
    fullname: G Alter
– volume: 10
  start-page: 2253
  issue: 7
  year: 2004
  ident: 2054_CR11
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-1087-3
  contributor:
    fullname: WL Gluck
– volume: 118
  start-page: 3347
  issue: 12
  year: 2011
  ident: 2054_CR14
  publication-title: Blood
  doi: 10.1182/blood-2011-05-351411
  contributor:
    fullname: S Veeramani
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Snippet In the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we...
Objective In the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we...
OBJECTIVEIn the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we...
Abstract Objective In the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA)....
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StartPage 277
SubjectTerms Analysis
ANCA-associated vasculitis
Antibodies
Antineoplastic agents
Arthritis
B cell depletion
B cells
Cloning
Cytotoxicity
Granulomatosis with polyangiitis
Health aspects
Immunoglobulins
Immunotherapy
Inflammatory diseases
Killer cells
Medical research
Monoclonal antibodies
Natural killer cells
Obinutuzumab
Penicillin
Rheumatic diseases
Rheumatoid arthritis
Rituximab
Software
Statistical analysis
Vasculitis
Vein & artery diseases
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Title Activation of natural killer cells by rituximab in granulomatosis with polyangiitis
URI https://www.ncbi.nlm.nih.gov/pubmed/31829278
https://www.proquest.com/docview/2328278508
https://search.proquest.com/docview/2325300916
https://pubmed.ncbi.nlm.nih.gov/PMC6907269
https://doaj.org/article/cecf829c83b049bcb9ae221678273532
Volume 21
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