ArticleBlood2020
Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome.
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Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30citing papers in PubMed
4.3field-weighted citation impact, top 4% of its field
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- Thromborepair: the tissue repair partner to thromboinflammation.Blood vessels, thrombosis & hemostasis · 2026Review
- Acquired Platelet Dysfunction with Eosinophilia: A Narrative Review.Pediatric reports · 2026Review
- Gray platelet syndrome as a multisystem disorder: immune dysregulation, autoimmunity, and metabolic abnormalities.Annals of hematology · 2026Article
- Molecular diagnosis of inherited platelet disorders: a tale of two realities - advanced vs. resource-limited setting.Thrombosis journal · 2025Review
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- Platelets as drivers of immunothrombosis in rheumatic diseases.Nature reviews. Rheumatology · 2025Review
- Mechanisms of exercise in preventing cardiovascular diseases: Insights from gut microbiota characteristics in pathological states of cardiovascular diseases.Reviews in endocrine & metabolic disorders · 2025Review
- Unveiling the Gray: A Rare Case of Gray Platelet Syndrome With Hepatomegaly and Immune Dysregulation in a 14-Year-Old.Case reports in hematology · 2025Article
- The Perspectives of Platelet Proteomics in Health and Disease.Biomedicines · 2024Review
- Article
- High-throughput microfluidic blood testing to phenotype genetically linked platelet disorders: an aid to diagnosis.Blood advances · 2023Article
- A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.Nature communications · 2023Article
- NBEAL2 deficiency in humans leads to low CTLA-4 expression in activated conventional T cells.Nature communications · 2023Article
- Article
- Mutations in Neurobeachin-like 2 do not impact Weibel-Palade body biogenesis and von Willebrand factor secretion in gray platelet syndrome Endothelial Colony Forming Cells.Research and practice in thrombosis and haemostasis · 2023Article
- The Analysis of the Human Megakaryocyte and Platelet Coding Transcriptome in Healthy and Diseased Subjects.International journal of molecular sciences · 2022Review
- Genetics of inherited thrombocytopenias.Blood · 2022Review
- Effects of ex vivo blood anticoagulation and preanalytical processing time on the proteome content of platelets.Journal of thrombosis and haemostasis : JTH · 2022Article
- Neutrophil transit time and localization within the megakaryocyte define morphologically distinct forms of emperipolesis.Blood advances · 2022Article
- Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation.International journal of molecular sciences · 2022Review
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Authors and funding
64 authors at 20 institutions in 12 countries.
Matthew C SimsDepartment of Haematology, University of Cambridge, and.
Louisa MayerDepartment of Haematology, University of Cambridge, and.
Janine H CollinsDepartment of Haematology, University of Cambridge, and.
Tadbir K BarianaDepartment of Haematology, University of Cambridge, and.
Karyn MegyDepartment of Haematology, University of Cambridge, and.
Cecile Lavenu-BombledAssistance Publique-Hôpitaux de Paris, Centre de Reference des Pathologies Plaquettaires, Hôpitaux Armand Trousseau, Bicêtre, Robert Debré, Paris, France.
Denis SeyresDepartment of Haematology, University of Cambridge, and.
Laxmikanth KolliparaLeibniz-Institut für Analytische Wissenschaften-ISAS-e. V., Dortmund, Germany.
Frances S BurdenDepartment of Haematology, University of Cambridge, and.
Daniel GreeneDepartment of Haematology, University of Cambridge, and.
Dave LeeStoller Biomarker Discovery Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Antonio Rodriguez-RomeraDepartment of Haematology, University of Cambridge, and.
Marie-Christine AlessiCentre for CardioVascular and Nutrition Research, INSERM 1263, INRAE 1260, Marseille, France.
William J AstleNational Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Wadie F BahouDepartment of Medicine, Stony Brook University, Stony Brook, NY.
Loredana BuryDepartment of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy.
Elizabeth ChalmersRoyal Hospital for Sick Children, Glasgow, United Kingdom.
Rachael Da SilvaStoller Biomarker Discovery Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Erica De CandiaInstitute of Internal Medicine and Geriatrics, Catholic University School of Medicine, Rome, Italy.
Sri V V DeeviDepartment of Haematology, University of Cambridge, and.
Samantha FarrowDepartment of Haematology, University of Cambridge, and.
Keith GomezRoyal Free London NHS Foundation Trust, London, United Kingdom.
Luigi GrassiDepartment of Haematology, University of Cambridge, and.
Andreas GreinacherInstitut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.
Paolo GreseleDepartment of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy.
Dan HartThe Royal London Hospital Haemophilia Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Marie-Françoise HurtaudAssistance Publique-Hôpitaux de Paris, Centre de Reference des Pathologies Plaquettaires, Hôpitaux Armand Trousseau, Bicêtre, Robert Debré, Paris, France.
Anne M KellyDepartment of Haematology, University of Cambridge, and.
Ron KerrDepartment of Haematology, Ninewells Hospital and Medical School, Dundee, United Kingdom.
Sandra Le QuellecService d'Hématologie Biologique, Hospices Civils de Lyon, Lyon, France.
Thierry LeblancAssistance Publique-Hôpitaux de Paris, Centre de Reference des Pathologies Plaquettaires, Hôpitaux Armand Trousseau, Bicêtre, Robert Debré, Paris, France.
Eva B LeinøeDepartment of Haematology, Rigshospitalet, Copenhagen, Denmark.
Rutendo MapetaDepartment of Haematology, University of Cambridge, and.
Harriet McKinneyDepartment of Haematology, University of Cambridge, and.
Alan D MichelsonCenter for Platelet Research Studies, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA.
Sara MoraisServiço de Hematologia Clínica, Hospital de Santo António, Centro Hospitalar Universitário do Porto, Porto, Portugal.
Diane NugentCenter for Inherited Bleeding Disorders, Children's Hospital of Orange County, Orange, CA.
Sofia PapadiaDepartment of Haematology, University of Cambridge, and.
Soo J ParkDivision of Hematology and Oncology, Moores Cancer Center, University of California, San Diego, La Jolla, CA.
John PasiThe Royal London Hospital Haemophilia Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Gian Marco PoddaUnità di Medicina 2, ASST Santi Paolo e Carlo, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.
Man-Chiu PoonUniversity of Calgary Cumming School of Medicine and Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, Calgary, AB, Canada.
Rachel ReedStoller Biomarker Discovery Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Mallika SekharDepartment of Haematology, Royal Free London NHS Trust, London, United Kingdom.
Hanna ShalevDepartment of Pediatric Hematology/Oncology, Soroka Medical Center, Faculty of Medicine, Ben-Gurion University, Beer Sheva, Israel.
Suthesh SivapalaratnamDepartment of Haematology, University of Cambridge, and.
Orna Steinberg-ShemerDepartment of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
Jonathan C StephensDepartment of Haematology, University of Cambridge, and.
Robert C TaitDepartment of Haematology, Royal Infirmary, Glasgow, United Kingdom.
Ernest TurroDepartment of Haematology, University of Cambridge, and.
John K M WuDivision of Hematology-Oncology, University of British Columbia and BC Children's Hospital, Vancouver, BC, Canada.
Barbara ZiegerDivision of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center-Faculty of Medicine, University of Freiburg, Freiburg, Germany.
NIHR BioResource
Taco W KuijpersDepartment of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Anthony D WhettonStoller Biomarker Discovery Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Albert SickmannLeibniz-Institut für Analytische Wissenschaften-ISAS-e. V., Dortmund, Germany.
Kathleen FresonDepartment of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
Kate DownesDepartment of Haematology, University of Cambridge, and.
Wendy N ErberFaculty of Health and Medical Sciences, The University of Western Australia, Crawley, Australia.
Mattia FrontiniDepartment of Haematology, University of Cambridge, and.
Paquita NurdenInstitut Hospitalo-Universitaire L'Institut de Rythmologie et Modélisation Cardiaque, Plateforme Technologique d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France.
Willem H OuwehandDepartment of Haematology, University of Cambridge, and.
Remi FavierAssistance Publique-Hôpitaux de Paris, Centre de Reference des Pathologies Plaquettaires, Hôpitaux Armand Trousseau, Bicêtre, Robert Debré, Paris, France.
Jose A GuerreroDepartment of Haematology, University of Cambridge, and.
National Health Service · GBUniversity of Cambridge · GBManchester Academic Health Science Centre · GBHôpital Armand-Trousseau · FRRoyal Free London NHS Foundation Trust · GBQueen Mary University of London · GBUniversity of Aberdeen · GBUniversity of Perugia · ITBarts Health NHS Trust · GBChildren's Hospital of Orange County · USGlasgow Royal Infirmary · GBHarvard University · USHospices Civils de Lyon · FRInserm · FRLeibniz Institute for Analytical Sciences - ISAS · DENinewells Hospital · GBRigshospitalet · DKRoyal Hospital for Children · GBSanquin · NLSoroka Medical Center · IL
Funding
Platelet Systems Biology in Health and DiseaseR01HL119096 · NHLBI · STATE UNIVERSITY NEW YORK STONY BROOK · PI BAHOU, WADIE F · 2015 to 2019
$3.5MMolecular characterization of biliverdin IXbeta reductaseR01HL153144 · NHLBI · STATE UNIVERSITY NEW YORK STONY BROOK · PI BAHOU, WADIE F · 2021 to 2024
$2.0MBritish Heart Foundation FS/18/53/33863Medical Research Council MR/M008959/1Medical Research Council MR/N00583X/1Medical Research Council MR/P02002X/1Medical Research Council MR/R002363/1NHLBI NIH HHS R01 HL119096NHLBI NIH HHS R01 HL153144Wellcome Trust
Abstract
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.
Indexed as
Genetic HeterogeneityGray Platelet SyndromePhenotypeBiopsyBlood ProteinsCase-Control StudiesCohort StudiesCytoplasmic GranulesDiagnosis, DifferentialGene FrequencyGenetic Association StudiesHumansImmune SystemImmune System DiseasesMutationBlood ProteinsNBEAL2 protein, human
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