The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and severity of, chronic ITP

Background: T-helper cell type 1 (Th1) polarization in chronic immune thrombocytopenia (cITP) has been reported at the protein and mRNA levels. We evaluated the impact of Th1/Th2 cytokine and cytokine receptor functional polymorphisms on both susceptibility to, and severity of, cITP. We analysed IFN-gamma + 874 T/A, IFN-gamma R -611G/A, IL-4 -590C/T, and IL-4R alpha Q576R polymorphisms in 126 cITP patients (male/female: 34/92; median age: 47.7 years) and 202 healthy control donors. Genotyping was determined by PCR and direct sequencing. The Th1/Th2 ratio was detected in peripheral blood mononuclear cells via flow cytometry. Results: cITP patients had a higher frequency of the IL-4R alpha 576 non-QQ genotype compared to healthy subjects (P = 0.04). cITP patients with the IFN-gamma + 874 non-AA genotype (high expression type) showed more severe thrombocytopenia than those with the AA genotype (P < 0.05). cITP patients had a significantly higher Th1/Th2 ratio than control patients (P < 0.01); this ratio was inversely correlated with platelet counts. Furthermore, patients with both IFN-gamma + 874 non-AA genotype (high expression type) and IFN-gamma R -611 non-AA genotype (high-function type) had a significantly higher Th1/Th2 ratio (P < 0.05). Conclusions: The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and severity of, chronic ITP.