Correlation of platelet FcγRIIA polymorphism in refractory idiopathic (immune) thrombocytopenic purpura

Abstract

Summary. FcgRIIA, a low affinity receptor for IgG, is a polymorphic molecule: FcgRIIA-HH131, FcgRIIA-HR131 and FcgRIIA-RR131. This polymorphism influences the efficiency of the receptor to bind with IgG2. Recent reports on altered distribution amongst individuals with heparininduced thrombocytopenia (HIT) prompted us to examine the FcgRIIA polymorphism in a cohort of patients with refractory idiopathic (immune) thrombocytopenic purpura (ITP), in whom severe disease had required them to undergo splenectomy. 29 post splenectomy ITP individuals and 61 normal controls were investigated. Polymerase chain reaction (PCR) and a Southern blotting technique were used to determine the FcgRII polymorphism. Although the distribution of the allotypes of FcgRIIA in the control population was similar to that found in other European studies of Caucasian populations (15 (25%) HH131; 35 (57%) HR131; 11(18%) RR131), the patient group was skewed towards the RR131 allotype which has least efficiency for IgG2 binding (3 (10%) HH131; 12 (42%) HR131; 14 (48%) RR131; P < 0·005). These findings suggest that FcgRIIA polymorphisms may be implicated in the pathophysiology of ITP or may be responsible for modulating the immune response in this heterogenous autoimmune disease.

Human Fc Receptors: Critical Targets in the Treatment of Autoimmune Diseases and Transplant Rejections

“…Among adult patients with refractory idiopathic thrombocytic purpura, relative enrichment of Fc␥RIIA-R131/R131 genotype was observed. These findings suggest that impaired processing of immune complexes underlies the pathogenesis of idiopathic thrombocytic purpura [35].…”

Antiplatelet Antibodies and Their Correlation with Clinical Findings in Childhood Immune Thrombocytopenic Purpura

“…It has been found that expression of Fcγ receptors on macrophages was higher in ITP patients than healthy controls. With this finding, it has been hypothesized that the presence of this polymorphism might affect the severity and chronicity of thrombocytopenia [9]. …”

Autoimmune Thrombocytopenia

“…Furthermore in the RR131 group, the male patients were older than the female patients. It is also known that among adults, ITP is more frequent in young women, 70% of female patients being under 40 years of age (George et al, 1994 (Williams et al, 1998; Table 5). …”

“…Both automated DNA sequence analysis and a single-strand conformation polymorphism assay have been used after polymerase chain reaction (PCR) amplification of a 278-base pair (bp) FcγRIIA-specific fragment (Reilly et al, 1994). The method used after FcγRIIA-specific PCR amplification, allele-specific oligonucleotide hybridisation is probably the most widely used, since it was first introduced as an easily adaptable genotyping method (Osborne et al, 1994;Brandt et al, 1995;Burgess et al, 1995;Salmon et al, 1996;Williams et al, 1998). Bachelot et al (1995) used denaturing gradient gel electrophoresis and DNA sequencing of single-strand templates.…”