Abstract
BackgroundT-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-γ + 874 T/A, IFN-γR -611G/A, IL-4 -590C/T, and IL-4Rα 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.ResultscITP patients had a higher frequency of the IL-4Rα 576 non-QQ genotype compared to healthy subjects (P = 0.04). cITP patients with the IFN-γ +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-γ +874 non-AA genotype (high expression type) and IFN-γR −611 non-AA genotype (high-function type) had a significantly higher Th1/Th2 ratio (P < 0.05).ConclusionsThe cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and severity of, chronic ITP.
Highlights
T-helper cell type 1 (Th1) polarization in chronic immune thrombocytopenia has been reported at the protein and mRNA levels
Recent studies have revealed that T helper (Th) type 1 (Th1) cytokine polarization occurs in chronic immune thrombocytopenia (cITP) patients [2,3,4,5]; several investigators have reported that the Th1/T-helper cell type 2 (Th2) ratio is inversely correlated with disease progression [3]
Patients with cITP had a significantly lower frequency of the IL-4Rα 576 QQ genotype compared to healthy controls using a dominant model (69.8% vs. 79.7% respectively, odds ratio [Odds ratio (OR)] = 0.59, 95% confidence interval [Confidence interval (CI)] = 0.35–0.98, P = 0.04)
Summary
T-helper cell type 1 (Th1) polarization in chronic immune thrombocytopenia (cITP) has been reported at the protein and mRNA levels. Recent studies have revealed that T helper (Th) type 1 (Th1) cytokine polarization occurs in cITP patients [2,3,4,5]; several investigators have reported that the Th1/Th2 ratio is inversely correlated with disease progression [3]. It was reported that serum levels of IL-4 were decreased in cITP patients [9, 10]. Such findings demonstrate that Th1 polarization is consistent with characteristics of cITP. It remains unclear whether the influences of Th1/Th2 cytokines on cITP are due to genetic factors
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