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

Blood
M. C. SimsJose A Guerrero

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 increas...Continue Reading

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Citations

Oct 23, 2020·Blood·A Koneti Rao, Deepak A Rao
Dec 11, 2020·Journal of Thrombosis and Haemostasis : JTH·Fred G Pluthero, Walter H A Kahr
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Mar 7, 2021·Journal of Clinical Medicine·Alessandro AliottaLorenzo Alberio
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May 1, 2021·International Journal of Molecular Sciences·Verónica Palma-BarquerosJosé Rivera
May 6, 2021·International Journal of Molecular Sciences·Olga ShevchukAlbert Sickmann
Jul 9, 2021·Stem Cell Research·Cathelijn E M AartsEmile van den Akker
Aug 6, 2021·Blood·Ulrike Seifert, Andreas Greinacher
Aug 20, 2021·Journal of Blood Medicine·Ana C GlembotskyPaula G Heller

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