Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Department of Hematology, Weihai Municipal Hospital, Weihai 264200, China.
J Immunol Res. 2018 Jul 22;2018:8170436. doi: 10.1155/2018/8170436. eCollection 2018.
The NLRP3 inflammasome plays important roles in the pathogenesis of autoimmune diseases. However, the role of the NLRP3 inflammasome in the pathophysiology of immune thrombocytopenia (ITP) remains unclear.
RT-PCR was used to examine the polymorphism and expression of genes involved in the NLRP3 inflammasome in ITP patients. T helper cells and apoptosis of PBMC from ITP patients were analyzed by flow cytometry. The antiplatelet autoantibodies in plasma were determined by modified monoclonal antibody-specific immobilization of platelet antigens (MAIPA).
We found that the NF-B-94ins/del ATTG genotype contributed to the susceptibility of ITP. Furthermore, the platelet counts of ITP patients with the WW genotype or WD genotype were lower than those with the DD genotype of NF-B-94ins/del ATTG. Compared with controls, NF-B gene expression was significantly decreased and WW or WD genotype ITP patients displayed higher mRNA expression than DD individuals. Similarly, the mRNA expression of NLRP3 was also increased in the WW genotype. There was a significant gene dose effect of the percentage of Th17 cells for the WW, WD, and DD genotypes (WW < WD < DD) in the unstimulated group and no significant difference was found after being stimulated. The activation of the NLRP3 inflammasome could upregulate Th17 in ITP patients.
The NF-B-94ins/del ATTG genotype might serve as a novel biomarker and potential target for ITP.
NLRP3 炎性小体在自身免疫性疾病的发病机制中发挥重要作用。然而，NLRP3 炎性小体在免疫性血小板减少症（ITP）的病理生理学中的作用尚不清楚。
采用 RT-PCR 检测 ITP 患者中涉及 NLRP3 炎性小体的基因多态性和表达。通过流式细胞术分析 ITP 患者的辅助性 T 细胞和 PBMC 的凋亡。通过改良的单克隆抗体特异性血小板抗原固定（MAIPA）测定血浆中的抗血小板自身抗体。
我们发现 NF-B-94ins/del ATTG 基因型与 ITP 的易感性有关。此外，WW 基因型或 WD 基因型的 ITP 患者的血小板计数低于 NF-B-94ins/del ATTG 的 DD 基因型。与对照组相比，NF-B 基因表达明显降低，WW 或 WD 基因型的 ITP 患者的 mRNA 表达高于 DD 个体。同样，WW 基因型中 NLRP3 的 mRNA 表达也增加。在未刺激组中，WW、WD 和 DD 基因型（WW<WD<DD）的 Th17 细胞的百分比存在显著的基因剂量效应，而在刺激后则没有发现差异。NLRP3 炎性小体的激活可上调 ITP 患者的 Th17。
NF-B-94ins/del ATTG 基因型可能作为 ITP 的新型生物标志物和潜在靶点。
