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Neutrophil specific granule and NETosis defects in gray platelet syndrome. / Aarts, Cathelijn E. M.; Downes, Kate; Hoogendijk, Arie J. et al.

In: Blood advances, Vol. 5, No. 2, 26.01.2021, p. 549-564.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

Aarts, CEM, Downes, K, Hoogendijk, AJ, Sprenkeler, EGG, Gazendam, RP, Favier, R, Favier, M, Tool, ATJ, van Hamme, JL, Kostadima, MA, Waller, K, Zieger, B, van Bergen, MGJM, Langemeijer, SMC, van der Reijden, BA, Janssen, H, van den Berg, TK, van Bruggen, R, Meijer, AB, Ouwehand, WH & Kuijpers, TW 2021, 'Neutrophil specific granule and NETosis defects in gray platelet syndrome', Blood advances, vol. 5, no. 2, pp. 549-564. https://doi.org/10.1182/bloodadvances.2020002442

APA

Aarts, C. E. M., Downes, K., Hoogendijk, A. J., Sprenkeler, E. G. G., Gazendam, R. P., Favier, R., Favier, M., Tool, A. T. J., van Hamme, J. L., Kostadima, M. A., Waller, K., Zieger, B., van Bergen, M. G. J. M., Langemeijer, S. M. C., van der Reijden, B. A., Janssen, H., van den Berg, T. K., van Bruggen, R., Meijer, A. B., ... Kuijpers, T. W. (2021). Neutrophil specific granule and NETosis defects in gray platelet syndrome. Blood advances, 5(2), 549-564. https://doi.org/10.1182/bloodadvances.2020002442

Vancouver

Aarts CEM, Downes K, Hoogendijk AJ, Sprenkeler EGG, Gazendam RP, Favier R et al. Neutrophil specific granule and NETosis defects in gray platelet syndrome. Blood advances. 2021 Jan 26;5(2):549-564. doi: 10.1182/bloodadvances.2020002442

Author

Aarts, Cathelijn E. M. ; Downes, Kate ; Hoogendijk, Arie J. et al. / Neutrophil specific granule and NETosis defects in gray platelet syndrome. In: Blood advances. 2021 ; Vol. 5, No. 2. pp. 549-564.

BibTeX

@article{5aab3193e5c0491f9af0925dcc33cdc7,
title = "Neutrophil specific granule and NETosis defects in gray platelet syndrome",
abstract = "Gray platelet syndrome (GPS) is an autosomal recessive bleeding disorder characterized by a lack of a-granules in platelets and progressive myelofibrosis. Rare loss-of-function variants in neurobeachin-like 2 (NBEAL2), a member of the family of beige and Ch{\'e}diak-Higashi (BEACH) genes, are causal of GPS. It is suggested that BEACH domain containing proteins are involved in fusion, fission, and trafficking of vesicles and granules. Studies in knockout mice suggest that NBEAL2 may control the formation and retention of granules in neutrophils. We found that neutrophils obtained from the peripheral blood from 13 patients with GPS have a normal distribution of azurophilic granules but show a deficiency of specific granules (SGs), as confirmed by immunoelectron microscopy and mass spectrometry proteomics analyses. CD341 hematopoietic stem cells (HSCs) from patients with GPS differentiated into mature neutrophils also lacked NBEAL2 expression but showed similar SG protein expression as control cells. This is indicative of normal granulopoiesis in GPS and identifies NBEAL2 as a potentially important regulator of granule release. Patient neutrophil functions, including production of reactive oxygen species, chemotaxis, and killing of bacteria and fungi, were intact. NETosis was absent in circulating GPS neutrophils. Lack of NETosis is suggested to be independent of NBEAL2 expression but associated with SG defects instead, as indicated by comparison with HSC-derived neutrophils. Since patients with GPS do not excessively suffer from infections, the consequence of the reduced SG content and lack of NETosis for innate immunity remains to be explored.",
author = "Aarts, {Cathelijn E. M.} and Kate Downes and Hoogendijk, {Arie J.} and Sprenkeler, {Evelien G. G.} and Gazendam, {Roel P.} and Remi Favier and Marie Favier and Tool, {Anton T. J.} and {van Hamme}, {John L.} and Kostadima, {Myrto A.} and Kate Waller and Barbara Zieger and {van Bergen}, {Maaike G. J. M.} and Langemeijer, {Saskia M. C.} and {van der Reijden}, {Bert A.} and Hans Janssen and {van den Berg}, {Timo K.} and {van Bruggen}, Robin and Meijer, {Alexander B.} and Ouwehand, {Willem H.} and Kuijpers, {Taco W.}",
note = "Funding Information: The patients with GPS were enrolled in the National Institute for Health Research (NIHR) BioResource Rare Diseases and their DNA analyzed by the associated BRIDGE genome sequencing projects. Both initiatives are supported by the NIHR (http://www.nihr.ac.uk). Research in the Ouwehand laboratory is supported by grants from the European Commission, NIHR, and the British Heart Foundation (RP-PG-0310-1002 and RG/09/12/28096). The laboratory also receives funding from NHS Blood and Transplant. K.D. is funded as a Higher Specialist Scientist Training (HSST) trainee by Health Funding Information: Education England. R.P.G. was supported by the Landsteiner Foundation for Blood Transfusion Research (LSBR 1706) awarded to T.W.K. C.E.M. was supported by the Sanquin Blood Supply Product and Process Development Cellular Products Fund (PPOC 2089). Publisher Copyright: {\textcopyright} 2021 by The American Society of Hematology.",
year = "2021",
month = jan,
day = "26",
doi = "10.1182/bloodadvances.2020002442",
language = "English",
volume = "5",
pages = "549--564",
journal = "Blood advances",
issn = "2473-9529",
publisher = "American Society of Hematology",
number = "2",

}

RIS

TY - JOUR

T1 - Neutrophil specific granule and NETosis defects in gray platelet syndrome

AU - Aarts, Cathelijn E. M.

AU - Downes, Kate

AU - Hoogendijk, Arie J.

AU - Sprenkeler, Evelien G. G.

AU - Gazendam, Roel P.

AU - Favier, Remi

AU - Favier, Marie

AU - Tool, Anton T. J.

AU - van Hamme, John L.

AU - Kostadima, Myrto A.

AU - Waller, Kate

AU - Zieger, Barbara

AU - van Bergen, Maaike G. J. M.

AU - Langemeijer, Saskia M. C.

AU - van der Reijden, Bert A.

AU - Janssen, Hans

AU - van den Berg, Timo K.

AU - van Bruggen, Robin

AU - Meijer, Alexander B.

AU - Ouwehand, Willem H.

AU - Kuijpers, Taco W.

N1 - Funding Information: The patients with GPS were enrolled in the National Institute for Health Research (NIHR) BioResource Rare Diseases and their DNA analyzed by the associated BRIDGE genome sequencing projects. Both initiatives are supported by the NIHR (http://www.nihr.ac.uk). Research in the Ouwehand laboratory is supported by grants from the European Commission, NIHR, and the British Heart Foundation (RP-PG-0310-1002 and RG/09/12/28096). The laboratory also receives funding from NHS Blood and Transplant. K.D. is funded as a Higher Specialist Scientist Training (HSST) trainee by Health Funding Information: Education England. R.P.G. was supported by the Landsteiner Foundation for Blood Transfusion Research (LSBR 1706) awarded to T.W.K. C.E.M. was supported by the Sanquin Blood Supply Product and Process Development Cellular Products Fund (PPOC 2089). Publisher Copyright: © 2021 by The American Society of Hematology.

PY - 2021/1/26

Y1 - 2021/1/26

N2 - Gray platelet syndrome (GPS) is an autosomal recessive bleeding disorder characterized by a lack of a-granules in platelets and progressive myelofibrosis. Rare loss-of-function variants in neurobeachin-like 2 (NBEAL2), a member of the family of beige and Chédiak-Higashi (BEACH) genes, are causal of GPS. It is suggested that BEACH domain containing proteins are involved in fusion, fission, and trafficking of vesicles and granules. Studies in knockout mice suggest that NBEAL2 may control the formation and retention of granules in neutrophils. We found that neutrophils obtained from the peripheral blood from 13 patients with GPS have a normal distribution of azurophilic granules but show a deficiency of specific granules (SGs), as confirmed by immunoelectron microscopy and mass spectrometry proteomics analyses. CD341 hematopoietic stem cells (HSCs) from patients with GPS differentiated into mature neutrophils also lacked NBEAL2 expression but showed similar SG protein expression as control cells. This is indicative of normal granulopoiesis in GPS and identifies NBEAL2 as a potentially important regulator of granule release. Patient neutrophil functions, including production of reactive oxygen species, chemotaxis, and killing of bacteria and fungi, were intact. NETosis was absent in circulating GPS neutrophils. Lack of NETosis is suggested to be independent of NBEAL2 expression but associated with SG defects instead, as indicated by comparison with HSC-derived neutrophils. Since patients with GPS do not excessively suffer from infections, the consequence of the reduced SG content and lack of NETosis for innate immunity remains to be explored.

AB - Gray platelet syndrome (GPS) is an autosomal recessive bleeding disorder characterized by a lack of a-granules in platelets and progressive myelofibrosis. Rare loss-of-function variants in neurobeachin-like 2 (NBEAL2), a member of the family of beige and Chédiak-Higashi (BEACH) genes, are causal of GPS. It is suggested that BEACH domain containing proteins are involved in fusion, fission, and trafficking of vesicles and granules. Studies in knockout mice suggest that NBEAL2 may control the formation and retention of granules in neutrophils. We found that neutrophils obtained from the peripheral blood from 13 patients with GPS have a normal distribution of azurophilic granules but show a deficiency of specific granules (SGs), as confirmed by immunoelectron microscopy and mass spectrometry proteomics analyses. CD341 hematopoietic stem cells (HSCs) from patients with GPS differentiated into mature neutrophils also lacked NBEAL2 expression but showed similar SG protein expression as control cells. This is indicative of normal granulopoiesis in GPS and identifies NBEAL2 as a potentially important regulator of granule release. Patient neutrophil functions, including production of reactive oxygen species, chemotaxis, and killing of bacteria and fungi, were intact. NETosis was absent in circulating GPS neutrophils. Lack of NETosis is suggested to be independent of NBEAL2 expression but associated with SG defects instead, as indicated by comparison with HSC-derived neutrophils. Since patients with GPS do not excessively suffer from infections, the consequence of the reduced SG content and lack of NETosis for innate immunity remains to be explored.

UR - http://www.scopus.com/inward/record.url?scp=85099805726&partnerID=8YFLogxK

U2 - 10.1182/bloodadvances.2020002442

DO - 10.1182/bloodadvances.2020002442

M3 - Article

C2 - 33496751

VL - 5

SP - 549

EP - 564

JO - Blood advances

JF - Blood advances

SN - 2473-9529

IS - 2

ER -

ID: 15496036