Takahashi Noriyuki, Saitoh Takayuki, Gotoh Nanami, Nitta Yasuhiro, Alkebsi Lobna, Kasamatsu Tetsuhiro, Minato Yusuke, Yokohama Akihiko, Tsukamoto Norifumi, Handa Hiroshi, Murakami Hirokazu
Graduate School of Health Sciences, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8514, Japan.
Department of Virology and Preventive Medicine, Gunma University, Gunma, Japan.
BMC Immunol. 2017 May 16;18(1):26. doi: 10.1186/s12865-017-0210-3.
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-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.
cITP 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).
The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and severity of, chronic ITP.
慢性免疫性血小板减少症（cITP）中辅助性T细胞1型（Th1）极化现象已在蛋白质和mRNA水平上被报道。我们评估了Th1/Th2细胞因子及细胞因子受体功能多态性对cITP易感性和严重程度的影响。我们分析了126例cITP患者（男/女：34/92；中位年龄：47.7岁）和202名健康对照者的IFN-γ +874 T/A、IFN-γR -611G/A、IL-4 -590C/T和IL-4Rα Q576R多态性。通过聚合酶链反应（PCR）和直接测序进行基因分型。通过流式细胞术检测外周血单个核细胞中的Th1/Th2比值。
与健康受试者相比，cITP患者中IL-4Rα 576非QQ基因型的频率更高（P = 0.04）。具有IFN-γ +874非AA基因型（高表达型）的cITP患者比具有AA基因型的患者表现出更严重的血小板减少（P < 0.05）。cITP患者的Th1/Th2比值显著高于对照患者（P < 0.01）；该比值与血小板计数呈负相关。此外，同时具有IFN-γ +874非AA基因型（高表达型）和IFN-γR -611非AA基因型（高功能型）的患者的Th1/Th2比值显著更高（P < 0.05）。
影响Th1/Th2的细胞因子多态性增加了慢性ITP的易感性和严重程度。
