PUBLICATION
Severe gastrointestinal bleeding and thrombocytopenia in a child with an anti-GATA1 autoantibody
- Authors
- de Waele, L., Freson, K., Louwette, S., Thys, C., Wittevrongel, C., de Vos, R., Debeer, A., and van Geet, C.
- ID
- ZDB-PUB-091120-73
- Date
- 2010
- Source
- Pediatric Research 67(3): 314-319 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Autoantibodies/blood*
- Autoimmunity*
- Cells, Cultured
- Child, Preschool
- Female
- GATA1 Transcription Factor/genetics
- GATA1 Transcription Factor/immunology*
- Gastrointestinal Hemorrhage/blood
- Gastrointestinal Hemorrhage/immunology*
- Gastrointestinal Hemorrhage/therapy
- Gastrointestinal Neoplasms/blood
- Gastrointestinal Neoplasms/immunology*
- Gastrointestinal Neoplasms/therapy
- Hemangioma/blood
- Hemangioma/immunology*
- Humans
- Infant, Newborn
- Lymphocytes/immunology
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Platelet Count
- Severity of Illness Index
- Thrombocytopenia/blood
- Thrombocytopenia/immunology*
- Thrombocytopenia/therapy
- Thrombopoiesis
- Transfection
- Zebrafish/genetics
- PubMed
- 19924028 Full text @ Pediatr. Res.
Citation
de Waele, L., Freson, K., Louwette, S., Thys, C., Wittevrongel, C., de Vos, R., Debeer, A., and van Geet, C. (2010) Severe gastrointestinal bleeding and thrombocytopenia in a child with an anti-GATA1 autoantibody. Pediatric Research. 67(3):314-319.
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. Allo-immune thrombocytopenia was excluded. Only 3 years 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 immunoglobulins (Ig) and recombinant GATA1, GATA2 and the N-finger 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 to control Igs. Mice injected with patient Igs showed a reduced platelet count compared to mice injected with control Igs. Thrombopoiesis was also reduced after injection of patient Igs in transgenic zebrafish compared to 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping