FcγR Ⅱ A And FcγRⅢa Polymorphism And Its Clinical Significance In The Chinese Patients With Immune Thrombocytopenic Purpura:a Preliminary Study

Background:Immune thrombocytopenic purpura is clinically characterized by bleeding diathesis and low platelet counts. It is well accepted that autoantibody-mediated phagocytosis of platelets is involved in the pathogenesis of ITP. Fab segments of platelet glycoprotein antibodies and immune circulation complex bind with platelets, then Fc segments of these antibodies bind with Fc receptors on the surface of human macrophages. Engagement of FcyR subclass FcγRⅡa and FcγRⅢa on the surface of human macrophages by antibodies-coated platelets triggers intracellular signaling that leads to engulfinent of the opsonized platelets. Single base mutation cause polymorphism of FcγRⅡa and FcγRⅢa. H/H, R/R and H/R genotypes are the three genotypes of FcγRⅡa. Genotypes of FcγRⅢa are F/F, V/V and F/V. Polymorphism of the two receptors may play a role in the pathogenesis of ITP. However, studies of Fc receptor polymorphism in ITP have different conclusions in different population.Objectives:1、To investigate the distribution frequencies of FcγRⅡa、FcγⅢa genotypes in patients with ITP and healthy population in China, and to elucidate the differences of FcγRⅡa、FcγRⅢa polymorphism gene in different population;2、To investigate the correlation between distribution frequencies of FcγRⅡa、FcγRⅢa genotypes and ANA, PAIgG, platelet counts, or courses of ITP.Methods:Allele-specific PCR were used to determine the genotypes of FcγR Ⅱa、FcγRⅢa gene in ITP (including primary and secondary) patients and control groups. PAIgG was determined by ELISA.Results:1.172ITP patients and191controls were included between the age of18-81years old, in which female were about70%.2. Frequencies of3genotypes of FcγRⅡa gene showed no significant differences in ITP and control groups, both in primary and secondary ITP. H/H genotype frequencies in the two groups were18.6%vs25.1%, R/R9.9%vs9.9%, H/R71.5%vs64.9%, P>0.05.2. Frequencies of FcγRⅡa H/H genotype in ANA-negative PITP patients was higher than in ANA-positive PITP patients, there was a significant differences between them (24.6%vs7.8%, P<0.05).3. There was no obvious correlation between frequencies of FcyR II a genotypes and PAIgG, platelet counts or the courses of PITP. Frequencies of H/H, R/R, H/R genotypes in≤12months group and>12months group were3.9%vs14.0%,11.1%vs9.3%,75.0%vs76.7%respectively, P>0.05.4. Frequencies of3genotypes of FcγRⅢa gene showed no significant differences between ITP and control groups, there were15.9%vs9.2%in F/F,9.1%vs5.7%in V/V,75.0%vs85.1%in F/V respectively, P>0.05. Also there were no correlation with ANA positive or not.5. Significant differences was showed between Chinese and other populations.Conclusions:1. Frequencies of FcyR II a gene genotypes showed no significant differences between ITP patients and control groups.2. Frequency of H/H genotype was higher in ANA-negative ITP patients than in ANA-positive ITP patients. It seems that H/H genotype plays a role in preventing immune complex deposition and weakening the inflammation in tissue.3. No obvious correlation between frequencies of FcγRⅡa genotypes and PAIgG, platelet counts and the courses of ITP.4. Frequencies of FcγRⅢa gene genotypes showed no significant differences in ITP and control groups, and also showed no correlation with ANA positive or not.