FcγRIIa and FcγRIIIa genetic polymorphisms in a group of pediatric immune thrombocytopenic purpura in Egypt

Abstract

Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder caused by the production of antiplatelet antibodies. The current case-control study aimed at detecting the frequency of FcγRIIa-131H/R and FcγRIIIa-158F/V genes polymorphism in Egyptian children with ITP as genetic markers for ITP risk, and to clear out their possible role in choosing the treatment protocols of ITP. To achieve this aim, FcγRIIa genotyping was tested by PCR-restriction fragment length polymorphism (RFLP) technique, whereas FcγRIIIa genotyping was tested by nested PCR followed RFLP analysis. The current case-control study was conducted on 92 children with ITP; 12 acute and 80 chronic cases and 90 controls. The V allele and FcγRIIIa FV heterotype were significantly higher in ITP patients and conferred increased ITP risk [odds ratio (OR) = 1.96 and 2.55, respectively]. The frequency of FcγRIIa H allele was significantly higher among chronic ITP patients. In conclusion, FcγRIIIa gene polymorphism may contribute to susceptibility to ITP. Moreover, analysis of the FcγR polymorphisms in ITP patients could influence the effectiveness of medications and selection of the line of treatment.

Cytokine gene polymorphism [tumor necrosis factor-alpha (–308), IL-10 (–1082), IL-6 (–174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities

“…Fujimoto et al [39] reported that FcgRIIIa FV heterotype predisposes to ineffective response to medications, and stated that FcgRIIIA polymorphism, but not FcgRIIA, may contribute to the different levels of clearance of antibody-sensitized platelets, which further supports the role of the FcgRIIIA polymorphism on the response to treatment in ITP. So, ITP patients with the V allele of FcgRIIIa will benefit the most from blockage of such high-affinity receptor by intravenous infusion of anti-D or they should be selected for the IVIG therapy [40].…”

Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis

“…[9][10][11][12][13][14][15][16]19,25,26,35,52,[55][56][57][58][59] Three polymorphisms (DNMT3B-579 T/ G, FcyRIIa-131 H/R, and FcyRIIIa-158 F/V) were analyzed in .1 study and did not show any significant differences. Of all other polymorphisms, analyzed in single studies only, 2 allele frequencies showed significantly higher risks for developing chronic ITP: TGF-B1 cod 25 allele A (OR 6.28; 95% CI 3.14-12.55) and IL-4 intron 3 allele RP1 (OR 3.95; 95% CI 1.29-12.09).…”

“…In 8 studies, the new definition of chronic ITP was used. 25,27,49,52,[55][56][57][58] However, assessment of forest plots comparing results of studies using the old definition vs the new definition for chronic ITP did not show any differences (data not shown).…”

“…Two studies analyzed the presence of platelet antibodies, and both did not find a significant difference (Figure 6). 25,52 Nielsen et al analyzed the presence of anti-glycoprotein antibodies and found significant less frequent anti-glycoprotein antibodies in patients who developed chronic disease (OR 0.11, 95% 0.01-0.84).…”

“…Two studies analyzed the presence of platelet antibodies, and both did not find a significant difference ( Figure 6). 25,52 Nielsen et al analyzed the presence of anti-glycoprotein antibodies and found significant less frequent anti-glycoprotein antibodies in patients who developed chronic disease (OR 0.11, 95% 0.01-0.84). 53 Yildirmak et al studied the percentage of platelet-associated immunoglobulin M and immunoglobulin G and found a significantly lower percentage of platelet-associated immunoglobulin M in patients who developed chronic ITP.…”