title: Proteomic analysis of platelet N-glycoproteins in PMM2-CDG patients.
abstract: PMM2-CDG, the most frequent congenital disorder of N-glycosylation, is an autosomal recessive disease with a multisystem presentation. PMM2-CDG patients show an increased risk for thrombosis, which might be in part due to spontaneous platelet aggregations as previously described. A potential hypoglycosylation of platelet proteins in these patients might explain this increased reactivity, as removal of sialic acid from platelets, particularly of GPIbα, leads to enhance platelet aggregation and clearance from the circulation. This study is the first one that has evaluated the glycosylation status of platelet proteins in 6 PMM2-CDG patients using different approaches including immunoblot, RCA120 lectin binding to platelets and expression of different membrane platelet N-glycoproteins by flow cytometry, as well as by platelet N-glycoproteome analysis. RCA120 lectin binding to the platelet membrane of PMM2-CDG patients showed evidence for decreased sialic acid content. However, immunoblot and flow cytometric analysis of different platelet N-glycoproteins, together with the more sensitive 2D-DIGE analysis, suggest that platelet N-glycoproteins, including GPIbα, seem to be neither quantitatively nor qualitatively significantly affected. The increased binding of RCA120 lectin could be explained by the abnormal glycosylation of hepatic proteins being attached to the platelets.
  
  
  CONCLUSIONS
  This is the first study that has evaluated the platelet N-glycoproteome. Our findings suggest that platelet proteins are not significantly affected in PMM2-CDG patients. Further studies are still warranted to unravel the mechanism(s) that increase(s) the risk of thrombosis in these patients.
authors.affiliation: Centro Regional de Hemodonación, Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, University of Murcia, Murcia, Spain.
authors.forename: M E
authors.initials: ME
authors.lastname: de la Morena-Barrio
authors.affiliation: Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Di Michele
authors.affiliation: Centro Regional de Hemodonación, Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, University of Murcia, Murcia, Spain.
authors.forename: M L
authors.initials: ML
authors.lastname: Lozano
authors.affiliation: Centro Regional de Hemodonación, Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, University of Murcia, Murcia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rivera
authors.affiliation: Departamento de Neurología Infantil, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Pérez-Dueñas
authors.affiliation: Unidad de Hemofilia, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Altisent
authors.affiliation: Department of Haematology, Centro Hospitalar de Coimbra, Portugal.
authors.forename: T
authors.initials: T
authors.lastname: Sevivas
authors.affiliation: Centro Regional de Hemodonación, Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, University of Murcia, Murcia, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Vicente
authors.affiliation: Center for Metabolic Diseases, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Jaeken
authors.affiliation: Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Freson
authors.affiliation: Centro Regional de Hemodonación, Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, University of Murcia, Murcia, Spain. Electronic address: javier.corral@carm.es.
authors.forename: J
authors.initials: J
authors.lastname: Corral
mesh_terms: D016022:Case-Control Studies; D018981:Congenital Disorders of Glycosylation / Q000097:blood*; D006031:Glycosylation; D006801:Humans; D010980:Platelet Membrane Glycoproteins / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics
chemical_list: D010980:Platelet Membrane Glycoproteins
keywords: Glycosylation; PMM2-CDG; Platelets; Proteomics