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

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.

• Authors: 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, Masja de Haas
• Journal: Blood advances (Blood Adv) Vol. 3 Issue 13 Pg. 2003-2012 (07 09 2019) ISSN: 2473-9537 [Electronic] United States
• PMID: 31270082 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 by The American Society of Hematology.

Chemical References

• Biomarkers
• Immunoglobulins, Intravenous
• Receptors, IgG

Topics

• Alleles
• Biomarkers
• Child
• Child, Preschool
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Immunoglobulins, Intravenous
• Male
• Odds Ratio
• Polymorphism, Genetic
• Purpura, Thrombocytopenic, Idiopathic (diagnosis, etiology, metabolism, therapy)
• Receptors, IgG (genetics, metabolism)
• Treatment Outcome