Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Relapse risk following truncation of pegylated asparaginase in childhood acute lymphoblastic leukemia

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Cost-effectiveness targeting CLL

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Sirolimus with CSP and MMF as GVHD prophylaxis for allogeneic transplantation with HLA antigen-mismatched donors

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. A novel homozygous GFI1B variant in 2 sisters with thrombocytopenia and severe bleeding tendency

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. A case of thrombocytopenia and multiple thromboses after vaccination with ChAdOx1 nCoV-19 against SARS-CoV-2

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Highly impaired platelet ultrastructure in two families with novel IKZF5 variants

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Blodsygdomme

    Research output: Chapter in Book/Report/Conference proceedingBook chapterEducationpeer-review

  • Matthew C Sims
  • Louisa Mayer
  • Janine H Collins
  • Tadbir K Bariana
  • Karyn Megy
  • Cecile Lavenu-Bombled
  • Denis Seyres
  • Laxmikanth Kollipara
  • Frances S Burden
  • Daniel Greene
  • Dave Lee
  • Antonio Rodriguez-Romera
  • Marie-Christine Alessi
  • William J Astle
  • Wadie F Bahou
  • Loredana Bury
  • Elizabeth Chalmers
  • Rachael Da Silva
  • Erica De Candia
  • Sri V V Deevi
  • Samantha Farrow
  • Keith Gomez
  • Luigi Grassi
  • Andreas Greinacher
  • Paolo Gresele
  • Dan Hart
  • Marie-Françoise Hurtaud
  • Anne M Kelly
  • Ron Kerr
  • Sandra Le Quellec
  • Thierry Leblanc
  • Eva B Leinøe
  • Rutendo Mapeta
  • Harriet McKinney
  • Alan D Michelson
  • Sara Morais
  • Diane Nugent
  • Sofia Papadia
  • Soo J Park
  • John Pasi
  • Gian Marco Podda
  • Man-Chiu Poon
  • Rachel Reed
  • Mallika Sekhar
  • Hanna Shalev
  • Suthesh Sivapalaratnam
  • Orna Steinberg-Shemer
  • Jonathan C Stephens
  • Robert C Tait
  • Ernest Turro
  • NIHR BioResource
View graph of relations

Gray platelet syndrome (GPS) is a rare recessive disorder caused by biallelic variants in NBEAL2 and characterized by bleeding symptoms, the absence of platelet α-granules, splenomegaly, and bone marrow (BM) fibrosis. Due to the rarity of GPS, it has been difficult to fully understand the pathogenic processes that lead to these clinical sequelae. To discern the spectrum of pathologic features, we performed a detailed clinical genotypic and phenotypic study of 47 patients with GPS and identified 32 new etiologic variants in NBEAL2. The GPS patient cohort exhibited known phenotypes, including macrothrombocytopenia, BM fibrosis, megakaryocyte emperipolesis of neutrophils, splenomegaly, and elevated serum vitamin B12 levels. Novel clinical phenotypes were also observed, including reduced leukocyte counts and increased presence of autoimmune disease and positive autoantibodies. There were widespread differences in the transcriptome and proteome of GPS platelets, neutrophils, monocytes, and CD4 lymphocytes. Proteins less abundant in these cells were enriched for constituents of granules, supporting a role for Nbeal2 in the function of these organelles across a wide range of blood cells. Proteomic analysis of GPS plasma showed increased levels of proteins associated with inflammation and immune response. One-quarter of plasma proteins increased in GPS are known to be synthesized outside of hematopoietic cells, predominantly in the liver. In summary, our data show that, in addition to the well-described platelet defects in GPS, there are immune defects. The abnormal immune cells may be the drivers of systemic abnormalities such as autoimmune disease.

Original languageEnglish
JournalBlood
Volume136
Issue number17
Pages (from-to)1956-1967
Number of pages12
ISSN0006-4971
DOIs
Publication statusPublished - 22 Oct 2020

ID: 62066862