The FCGR3A-V158F and FCGR2A-H131R polymorphisms are associated with clinical responses to therapeutic mAbs and with immune thrombocytopenic purpura (ITP).
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.
Our results confirmed that the combination of high-affinity FCGR2A-131H and FCGR3A-158V allele was more common in patients with ITP than in controls (55% versus 40%; p = 0.024).
Our data suggest that genotyping of the <i>FCGR2/3</i> locus may be useful for prognosis and guidance of treatment decisions in newly diagnosed childhood ITP.
On screening of additional IVIg-treated patient cohorts, we identified 6 FCGR2A(c.742+871A>G) allele-positive patients with Kawasaki disease (n = 208) and 1 patient with idiopathic thrombocytopenia (n = 93).None had adverse reactions to IVIg.
Moreover, ROS inhibition or blocking FcγRIIa attenuated the decrease in GPIbα surface expression, platelet activation and ROS generation (for blocking FcγRIIa) in ITP plasma-treated platelets.
In vitro cell-culture experiments showed that DXM could induce FcγRIIa and FcγRIIb expression in monocytes from ITP patients, with FcγRIIb at higher amplitudes.
Furthermore, subgroup analyses by type of disease revealed that FCGR2AH131R polymorphism was significantly associated with childhood-onset ITP, and FCGR3A F158V polymorphism was significantly associated with both childhood-onset and adult-onset ITP.
FcγRIIIa-158V was significantly overrepresented in children with ITP versus controls (P = 0.029), whereas no statistically significant difference was noted in FcγRIIa polymorphism distribution.
CONCLUSIONS Our findings indicate that CD16 158F>V polymorphism may contribute to the increased risk of ITP, whereas CD32 131H>R polymorphism may not be an important risk factor for ITP.
But in the subgroup analysis, a significant association between FCGRH131R polymorphism and ITP susceptibility was observed in Caucasian population of childhood-onset group for H vs. R (OR = 1.246, 95% CI 1.021-1.522, p = 0.031), HH vs. HR + RR (OR = 1.562, 95% CI 1.145-2.129, p = 0.005), HH vs. HR (OR = 1.598, 95% CI 1.146-2.228, p = 0.006), HH vs. RR (OR = 1.484, 95% CI 1.005-2.191, p = 0.047).