Transient and chronic childhood immune thrombocytopenia are distinctly affected by Fc-γ receptor polymorphisms
| Autor: | Annemieke G. Laarhoven, Masja de Haas, Gestur Vidarsson, Marrie C. A. Bruin, C. Ellen van der Schoot, Katja M. J. Heitink-Pollé, Sietse Q. Nagelkerke, David E. Schmidt, Taco W. Kuijpers, Barbera Veldhuisen, Leendert Porcelijn |
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| Přispěvatelé: | APH - Aging & Later Life, General Paediatrics, AII - Inflammatory diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, Landsteiner Laboratory, ARD - Amsterdam Reproduction and Development |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Genotype Clinical Trials and Observations Disease FCGR2B FCGR2A Gene Frequency immune system diseases hemic and lymphatic diseases Odds Ratio Journal Article Medicine Humans Genetic Predisposition to Disease Child Genotyping Alleles Genetic Association Studies Purpura Thrombocytopenic Idiopathic Polymorphism Genetic biology business.industry Receptors IgG Autoantibody Immunoglobulins Intravenous Hematology Odds ratio FCGR3B Treatment Outcome Child Preschool Immunology biology.protein Female Antibody business Biomarkers |
| Zdroj: | Blood, 3(13), 2003-2012. American Society of Hematology Blood advances, 3(13), 2003-2012. American Society of Hematology Blood Advances, 3(13), 2003. The American Society of Hematology |
| ISSN: | 2473-9529 |
| Popis: | In childhood immune thrombocytopenia (ITP), anti-platelet autoantibodies mediate platelet clearance through Fc-γ receptor (FcγR)–bearing phagocytes. In 75% to 90% of patients, the disease has a transient, self-limiting character. Here we characterized how polymorphisms of FcγR genes affect disease susceptibility, response to intravenous immunoglobulin (IVIg) treatment, and long-term recovery from childhood ITP. Genotyping of the FCGR2/3 locus was performed in 180 children with newly diagnosed ITP, 22 children with chronic ITP, and 180 healthy control children by multiplex ligation-dependent probe amplification. Children with newly diagnosed ITP were randomly assigned to a single administration of IVIg or observation, and followed for 1 year (Treatment With or Without IVIg for Kids With ITP [TIKI] trial). We defined transient ITP as a complete recovery (≥100 × 109/L) 3 months after diagnosis, including both self-limiting disease/IVIg responders and chronic ITP as absence of a complete recovery at 12 months. ITP susceptibility, as well as spontaneous recovery and response to IVIg, was associated with the genetic variants FCGR2C*ORF and FCGR2A*27W and the FCGR2B promoter variant 2B.4. These variants were overrepresented in patients with transient (N = 131), but not chronic (N = 43), disease. The presence of FCGR2C*ORF predisposed to transient ITP with an odds ratio of 4.7 (95% confidence interval, 1.9-14.3). Chronic ITP was associated with a deletion of FCGR2C/FCGR3B (copy number region 1) with an odds ratio of 6.2 (95% confidence interval, 1.8-24.7). Taken together, susceptibility to transient and chronic ITP is distinctly affected by polymorphic variants of FCGR2/3 genes. Our data suggest that genotyping of the FCGR2/3 locus may be useful for prognosis and guidance of treatment decisions in newly diagnosed childhood ITP. |
| Databáze: | OpenAIRE |
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