Transient and chronic childhood immune thrombocytopenia are distinctly affected by Fc-γ receptor polymorphisms

David E. Schmidt, Katja M. J. Heitink-Pollé, Annemieke G. Laarhoven, Marrie C. A. Bruin, Barbera Veldhuisen, Sietse Q. Nagelkerke, Taco W. Kuijpers, Leendert Porcelijn, C. Ellen van der Schoot, Gestur Vidarsson and Masja de Haas

Key Points

  • Polymorphisms of the FCGR2/3 locus are associated with susceptibility to childhood ITP and progression to chronic disease.

  • Genotyping of the FCGR2/3 locus may be helpful to determine prognosis and personalize treatment decisions in childhood ITP.


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.

  • Submitted February 22, 2019.
  • Accepted April 30, 2019.
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