School of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
Departments of Medicine, Tibet Nationalities University, Xianyang, China.
Front Immunol. 2021 Dec 7;12:758554. doi: 10.3389/fimmu.2021.758554. eCollection 2021.
Autoimmune uveitis is characterized by immune disorders of the eyes and the whole body and is often recurrent in young adults, but its pathogenesis is still unclear. IL-35 is an essential regulatory factor in many autoimmune diseases, which is produced by Breg cells and can induce Breg cells to regulate the immune response. The relationship between the expression and gene polymorphism of IL-35 and the immune status of patients with autoimmune uveitis has not been reported. The peripheral blood of the subjects was collected from patients with Behçet's Disease (BD) and those with Vogt-Koyanagi-Harada (VKH) syndrome. The percentage of immune cell subsets including B cells, DC, and T cells, and the expression of IL-35 in serum of these two kinds of disease were analyzed. And then, the associations between seven IL-35 single nucleotide polymorphism (SNP) sites and disease susceptibility, the immune status, the clinical characteristics, and the serum IL-35 levels were analyzed. Our results showed that the percentage of Breg cells was significantly decreased in the blood of patients with VKH syndrome compared to that of healthy controls. The levels of IL-35 in the serum of patients with VKH syndrome or BD patients were not changed significantly, compared to that of healthy controls. Furthermore, the associations between two subunits of IL-35 (IL-12p35 and EBI3) and BD or VKH patients were analyzed. We found that there was an association between the EBI3 rs428253 and the occurrence of BD. There was an association between the IL-12p35 rs2243131 and the low level of Breg cell of VKH patients. In addition, there were associations between the polymorphisms of EBI3 rs4740 and the occurrence of headache and tinnitus of VKH patients, respectively. And the genotype frequency of IL-12p35 rs2243115 was related to the concentration of serum IL-35 in patients with VKH syndrome. Thus, the specific SNP sites change of IL-35 were correlated to the immune disorders in uveitis. And they may also play a guiding role in the occurrence of clinical symptoms in patients with uveitis, especially for VKH syndrome.
自身免疫性葡萄膜炎的特征是眼部和全身的免疫紊乱，常发生于年轻成年人，但发病机制尚不清楚。IL-35 是许多自身免疫性疾病中必不可少的调节因子，由 Breg 细胞产生，可以诱导 Breg 细胞调节免疫反应。IL-35 的表达和基因多态性与自身免疫性葡萄膜炎患者的免疫状态之间的关系尚未报道。从 Behcet 病（BD）和 Vogt-Koyanagi-Harada（VKH）综合征患者中采集受试者的外周血，分析这两种疾病患者的免疫细胞亚群（包括 B 细胞、DC 和 T 细胞）的比例和血清中 IL-35 的表达。然后，分析了七个 IL-35 单核苷酸多态性（SNP）位点与疾病易感性、免疫状态、临床特征和血清 IL-35 水平的关系。我们的结果表明，与健康对照组相比，VKH 综合征患者血液中的 Breg 细胞比例显著降低。与健康对照组相比，VKH 综合征或 BD 患者血清中 IL-35 的水平没有明显变化。此外，还分析了 IL-35 的两个亚基（IL-12p35 和 EBI3）与 BD 或 VKH 患者之间的关系。我们发现 EBI3 的 rs428253 与 BD 的发生有关。IL-12p35 的 rs2243131 与 VKH 患者 Breg 细胞数量低有关。此外，EBI3 的 rs4740 多态性与 VKH 患者头痛和耳鸣的发生有关，IL-12p35 的 rs2243115 基因型频率与 VKH 患者血清中 IL-35 的浓度有关。因此，IL-35 的特定 SNP 位点的变化与葡萄膜炎中的免疫紊乱有关。它们也可能在葡萄膜炎患者的临床症状的发生中起指导作用，特别是对于 VKH 综合征。
