Fcγ receptor IIa and IIIa polymorphisms in childhood immune thrombocytopenic purpura

MD Carcao, VS Blanchette… - British journal of …, 2003 - Wiley Online Library
MD Carcao, VS Blanchette, CD Wakefield, D Stephens, J Ellis, K Matheson, GA Denomme
British journal of haematology, 2003Wiley Online Library
Fcγ receptor‐mediated destruction of autoantibody‐sensitized platelets is central to the
immune pathophysiology of childhood immune thrombocytopenic purpura (ITP). Allelic
variants exist among the random population for some Fcγ receptors. The variants represent
single nucleotide polymorphisms, leading to functional differences in the ability to bind
immunoglobulin (Ig) G or IgG subclasses. The genotypic frequencies for two Fcγ receptor
single nucleotide polymorphisms, FcγRIIa‐131 arginine (R) versus histidine (H) and FcγRIIIa …
Summary
Fcγ receptor‐mediated destruction of autoantibody‐sensitized platelets is central to the immune pathophysiology of childhood immune thrombocytopenic purpura (ITP). Allelic variants exist among the random population for some Fcγ receptors. The variants represent single nucleotide polymorphisms, leading to functional differences in the ability to bind immunoglobulin (Ig)G or IgG subclasses. The genotypic frequencies for two Fcγ receptor single nucleotide polymorphisms, FcγRIIa‐131 arginine (R) versus histidine (H) and FcγRIIIa‐158 valine (V) versus phenylalanine (F) were examined in 98 children diagnosed with childhood ITP. The genotype frequencies were compared with those of 130 healthy control subjects. Chi‐square analysis was used to determine whether the allelic frequencies of the high‐affinity receptor variants were associated with childhood ITP. Both the FcγRIIa‐131H and the FcγRIIIa‐158V were significantly over‐represented in children with ITP versus the control subjects (P‐values 0·03). The same statistical difference was noted with the combined FcγRIIa‐131H and FcγRIIIa‐158V allelic gene frequencies. There was no statistical difference between children who later developed chronic ITP compared with children with acute ITP, suggesting that additional factors are responsible for the development of the chronic form of the disease. These observations underscore the importance of Fcγ receptor‐mediated cell clearance in childhood ITP.
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