IMPLICATION OF HUMAN FC RECEPTORS POLYMORPHISM IN CHILDHOOD IMMUNE THROMBOCYTOPENIC PURPURA
Abstract
Immune thrombocytopenic purpura (ITP) is the most frequent form of autoimmune disease in childhood, characterized by thrombocytopenia (platelet count <150·109/L) with otherwise normal cell lineages. One of the main mechanisms is the platelet destruction by phagocytic cells, covered by human Fc receptors (FCGR). The FCR family involves 3 classes of receptors: FCGR1A, 1B, and 1C; FCGR2A, 2B, and 2C; FCGR3A and 3B, all present on chromosome 1q23-24. The response to ITP treatment may be influenced by the polymorphism of the FCGR3A gene, which contributes to different levels of destruction of antibody - bound platelets. Material and methods: We report the results of FCGR2/3 polymorphic genotypes in 16 children with ITP admitted at the “Sf. Maria” Emergency Children’s Hospital, Iasi, Romania, treated with corticosteroids, intravenous immunoglobulin (IVIg) or both, or conservative treatment, with a minimum of one year follow up. Results: We identified 9/16 patients with FCGR2C ORF haplotypes, 8 in heterozygous state and one in homozygous state, and 15/16 patients with FCGR2A-His166 variant. While it was previously reported that classical FCGR2C-ORF and 2B.4 variants correlate with the transient form of ITP and a good response to IVIg, in our sample it was present only in 3 patients, who had limited course of disease and a good response to IVIg. 5 patients were heterozygotes for FCGR2C-p.Gln62Trp, all of them developing an acute form, a good response to IVIg and no relapses. Furthermore, it has been demonstrated an association between FCGR genotypes characterized by increased immunoglobulin binding activity (FCGR3A allele V158 and FGCGR3B allele NA1) and chronic children ITP. In our study, only 2/16 patients express NA1 in homozygous state, one of them developing persistent ITP, while the other responded well to the treatment and did not relapse. Conclusions: Genetic influences contribute to the pathogenesis of ITP in children and response to IVIg. We evaluated the genetic risk factors in the FCGR2/3 locus that are associated with predisposition to limited course and a favorable response to IVIg in ITP in children. However, confirmation in a larger prospectively recruited cohort of children with ITP is needed.
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