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Blood Adv. 2019 Jul 9;3(13):2003-2012. doi: 10.1182/bloodadvances.2019000068.

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

Author information

1
Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands.
2
Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
3
Department of Pediatric Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
4
Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
5
Department of Immunohematology Diagnostics, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
6
Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands.
7
Department of Pediatric Hematology, Immunology and Infectious Disease, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
8
Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands; and.
9
Jon J van Rood Center for Clinical Transfusion Science and.
10
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands.

Abstract

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.

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