Eslami Mina, Rafiei Alireza, Baghbanian Seyed Mohammad, Fattahi Sadegh, Yazdani Zahra, Valadan Reza, Kardan Mostafa
Department of Immunology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, 4847191971, Sari, Iran.
Department of Neurology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Immunol Res. 2022 Feb;70(1):75-85. doi: 10.1007/s12026-021-09246-9. Epub 2021 Oct 27.
This study aimed to investigate the association between serum levels and polymorphic variants of IL-35 with susceptibility, clinical features, and disease severity in multiple sclerosis (MS) patients.This case-control study recruited 186 MS patients and 195 sex- and age-matched healthy controls. Serum levels and polymorphic variants of IL-35 were determined by ELISA and restriction fragment length polymorphism (RFLP)-PCR or high resolution melting (HRM) analysis methods, respectively. In addition, by in silico analysis, we evaluated the location and function of the polymorphism.Serum levels of IL-35 were significantly lower in the patients than those of healthy controls (49.3 ± 3.7 vs. 69.5 ± 7.8, p = 0.009). EBI3 rs4740 polymorphism of IL-35 was associated with 2.2-fold increased risk of MS susceptibility (95% CI, 1.3-3.9, p = 0.005). However, there were no differences in the genotype distribution and allele frequencies of IL-35 rs568408 between the patients and controls (p > 0.05). In silico results showed that variation in IL-12A and EBI3 may affect on protein pathways of the cells and different components of the immune system such as NF-κB and INF-γ.The results show that IL-35 polymorphisms might be a genetic risk factor for the development of MS.
本研究旨在探讨白细胞介素-35（IL-35）的血清水平和多态性变体与多发性硬化症（MS）患者易感性、临床特征及疾病严重程度之间的关联。这项病例对照研究招募了186例MS患者和195例年龄及性别匹配的健康对照者。分别采用酶联免疫吸附测定（ELISA）和限制性片段长度多态性（RFLP）-聚合酶链反应（PCR）或高分辨率熔解曲线（HRM）分析方法测定IL-35的血清水平和多态性变体。此外，通过计算机模拟分析，我们评估了该多态性的位置和功能。患者血清中IL-35水平显著低于健康对照者（49.3±3.7对69.5±7.8，p=0.009）。IL-35的EBI3 rs4740多态性与MS易感性风险增加2.2倍相关（95%置信区间，1.3 - 3.9，p=0.005）。然而，患者与对照者之间IL-35 rs568408的基因型分布和等位基因频率并无差异（p>0.05）。计算机模拟结果显示，IL-12A和EBI3的变异可能会影响细胞的蛋白质通路以及免疫系统的不同组成部分，如核因子κB（NF-κB）和干扰素γ（INF-γ）。结果表明，IL-35多态性可能是MS发病的一个遗传风险因素。
