title: Severe gastrointestinal bleeding and thrombocytopenia in a child with an anti-GATA1 autoantibody.
abstract: We describe a patient, who developed during the first week of life petechiae and hematomas caused by severe thrombocytopenia and gastrointestinal bleeding due to multiple small gastric hemangiomata. Bone marrow examination showed hypermegakaryocytosis and dysmegakaryopoiesis. Alloimmune thrombocytopenia was excluded. Only 3 y later, platelet counts normalized and bleedings disappeared but small skin hemangiomata remained. Electron microscopy showed enlarged round platelets with a paucity of alpha granules similar as in GATA1-deficient patients but no GATA1 mutation was found. Immunoblot analysis showed a strong interaction between patient Igs and recombinant GATA1, GATA2, and the N finger (Nf) of GATA1. The lymphocyte transformation test with recombinant GATA1Nf was positive. In vitro culturing of normal CD34 cells with purified patient Igs showed a decreased number of megakaryocyte colonies but an increased overall size of the colonies compared with control Igs. Mice injected with patient Igs showed a reduced platelet count compared with mice injected with control Igs. Thrombopoiesis was also reduced after injection of patient Igs in transgenic zebrafish compared with control Igs. In conclusion, this study is the first report of an anti-GATA1 autoantibody leading to severe thrombocytopenia and gastrointestinal bleeding from multiple pinpoint hemangiomata.
authors.affiliation: Department of Pediatrics, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: de Waele
authors.forename: Kathleen
authors.initials: K
authors.lastname: Freson
authors.forename: Sophie
authors.initials: S
authors.lastname: Louwette
authors.forename: Chantal
authors.initials: C
authors.lastname: Thys
authors.forename: Christine
authors.initials: C
authors.lastname: Wittevrongel
authors.forename: Rita
authors.initials: R
authors.lastname: de Vos
authors.forename: Anne
authors.initials: A
authors.lastname: Debeer
authors.forename: Chris
authors.initials: C
authors.lastname: van Geet
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000276:immunology*; D006471:Gastrointestinal Hemorrhage / Q000097:blood / Q000276:immunology* / Q000628:therapy; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy; D006391:Hemangioma / Q000097:blood / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010976:Platelet Count; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000097:blood / Q000276:immunology* / Q000628:therapy; D034061:Thrombopoiesis; D014162:Transfection; D015027:Zebrafish / Q000235:genetics
chemical_list: D001323:Autoantibodies; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human