Fc&ggr;RIIa and Fc&ggr;RIIIa polymorphisms in childhood primary immune thrombocytopenia: implications for disease pathogenesis and outcome

Primary immune thrombocytopenia (ITP) is the commonest acquired cause of bleeding in childhood. The aim of the present study was to evaluate the role of Fc&ggr;RIIa and Fc&ggr;RIIIa polymorphisms in the pathogenesis and therapeutic result of childhood ITP. The genotypic frequencies for two Fc&ggr; receptor single-nucleotide polymorphisms, Fc&ggr;RIIa-131 arginine (R) versus histidine (H) and Fc&ggr;RIIIa-158 valine (V) versus phenylalanine (F) were examined in 53 children diagnosed with ITP. The genotype frequencies were compared with those of 45 healthy controls. The association between the above frequencies and disease natural course as well as therapeutic result following intravenous immunoglobulin (IVIG) administration was investigated. Fc&ggr;RIIIa-158V was significantly overrepresented in children with ITP versus controls (P = 0.029), whereas no statistically significant difference was noted in Fc&ggr;RIIa polymorphism distribution. No statistically significant difference was noted in the above genotype frequencies’ distribution between children with newly diagnosed and chronic ITP, as well as with regards to the therapeutic result following IVIG administration. High-affinity Fc&ggr;RIIIa variant (158 V) is possibly implicated in disease susceptibility, but neither of the two Fc&ggr; receptor single-nucleotide polymorphisms seem to have any impact on chronicity or therapeutic effect of IVIG.

[1]  Drew Provan,et al.  International consensus report on the investigation and management of primary immune thrombocytopenia. , 2010, Blood.

[2]  J. George,et al.  Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. , 2009, Blood.

[3]  A. Lazarus,et al.  Role of Fcgamma receptors in the pathogenesis and treatment of idiopathic thrombocytopenic purpura. , 2003, Journal of pediatric hematology/oncology.

[4]  R. Westendorp,et al.  Evidence for non-random distribution of Fcγ receptor genotype combinations , 2003, Immunogenetics.

[5]  J. Freedman,et al.  Monoclonal IgG can ameliorate immune thrombocytopenia in a murine model of ITP: an alternative to IVIG. , 2003, Blood.

[6]  R. Geha,et al.  IgG Fc receptor polymorphisms in human disease: implications for intravenous immunoglobulin therapy. , 2003, The Journal of allergy and clinical immunology.

[7]  R. Geha,et al.  Desloratadine inhibit T-cell responses, airway inflamation, and bronchial hyperresponsiveness (BHR) in murine models of asthma , 2003 .

[8]  V. Blanchette,et al.  Fcγ receptor IIa and IIIa polymorphisms in childhood immune thrombocytopenic purpura , 2003 .

[9]  G. Buchanan,et al.  Grading of hemorrhage in children with idiopathic thrombocytopenic purpura. , 2002, The Journal of pediatrics.

[10]  T. Shimomura,et al.  Involvement of Fcγ receptor polymorphism in the therapeutic response of idiopathic thrombocytopenic purpura , 2001 .

[11]  C. Hack,et al.  Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia. , 2001, Blood.

[12]  S. Steinberg,et al.  Polymorphisms in inflammatory cytokines and Fcγ receptors in childhood chronic immune thrombocytopenic purpura: a pilot study , 2001, British journal of haematology.

[13]  J. G. Winkel,et al.  IgG receptor polymorphisms: risk factors for disease , 1998, Immunogenetics.

[14]  R. Kimberly,et al.  A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. , 1997, The Journal of clinical investigation.

[15]  D. Roos,et al.  FcγRIIIa-158V/F Polymorphism Influences the Binding of IgG by Natural Killer Cell FcγRIIIa, Independently of the FcγRIIIa-48L/R/H Phenotype , 1997 .

[16]  M. Fanger,et al.  Monoclonal antibody 197 (anti‐FcγRI) infusion in a patient with immune thrombocytopenia purpura (ITP) results in down‐modulation of FcγRI on circulating monocytes , 1996 .

[17]  P. Parren,et al.  On the interaction of IgG subclasses with the low affinity Fc gamma RIIa (CD32) on human monocytes, neutrophils, and platelets. Analysis of a functional polymorphism to human IgG2. , 1992, The Journal of clinical investigation.

[18]  J. V. D. van de Winkel,et al.  A single amino acid in the second Ig-like domain of the human Fc gamma receptor II is critical for human IgG2 binding. , 1991, Journal of immunology.

[19]  J. Hall,et al.  Comparison of intravenous gamma globulin and a monoclonal anti-Fc receptor antibody as inhibitors of immune clearance in vivo in mice. , 1986, The Journal of clinical investigation.

[20]  R. Kimberly,et al.  Treatment of refractory immune thrombocytopenic purpura with an anti-Fcγ-receptor antibody , 1986 .

[21]  V. Blanchette,et al.  Fcgamma receptor IIa and IIIa polymorphisms in childhood immune thrombocytopenic purpura. , 2003, British journal of haematology.

[22]  R. Westendorp,et al.  Evidence for non-random distribution of Fcgamma receptor genotype combinations. , 2003, Immunogenetics.

[23]  J. V. Ravetch,et al.  IgG Fc receptors. , 2001, Annual review of immunology.

[24]  T. Shimomura,et al.  Involvement of Fc gamma receptor polymorphism in the therapeutic response of idiopathic thrombocytopenic purpura. , 2001, British journal of haematology.

[25]  J. V. D. van de Winkel,et al.  IgG receptor polymorphisms: risk factors for disease , 1998, Immunogenetics.

[26]  D. Roos,et al.  Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. , 1997, Blood.

[27]  M. Poncz,et al.  Rapid detection of the Fc gamma RIIA-H/R 131 ligand-binding polymorphism using an allele-specific restriction enzyme digestion (ASRED). , 1996, Journal of immunological methods.

[28]  M. Fanger,et al.  Monoclonal antibody 197 (anti-Fc gamma RI) infusion in a patient with immune thrombocytopenia purpura (ITP) results in down-modulation of Fc gamma RI on circulating monocytes. , 1996, British Journal of Haematology.

[29]  M. Poncz,et al.  Rapid detection of the ligand-binding polymorphism using an allele-specific restriction enzyme digestion (ASRED) , 1996 .

[30]  R. Kimberly,et al.  Treatment of refractory immune thrombocytopenic purpura with an anti-Fc gamma-receptor antibody. , 1986, The New England journal of medicine.