Department of Biochemistry, Panjab University, Chandigarh, India.
Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Lupus. 2020 Dec;29(14):1831-1844. doi: 10.1177/0961203320959441. Epub 2020 Sep 30.
Systemic Lupus Erythematosus is an autoimmune disease with symptoms pervasive to all organ systems. It affects more females as compared to males (in the ratio 9:1). Oxidative stress plays a major role in the pathogenesis of SLE and other autoimmune diseases. In order to understand the relationship between cell specific oxidative stress and the severity of SLE, this research study involving the estimation of intracellular ROS accumulation in T and NK cell was conducted on SLE patients of North Indian Population. At the same time, to estimate anti-oxidant defense, Keap1 and Nrf2 levels were estimated in these cell types. The relationship between the expression of Killer immunoglobulin receptors i.e., KIR2DL4 & KIR3DL1 and oxidative stress was also evaluated as these receptors are imperative for the function and self-tolerance of NK cells.Oxidative stress was raised along with Keap1 and Nrf2 in T and NK cell subsets in SLE patients. The expression of KIR2DL4 was raised and that of KIR3DL1 was reduced in the NK cells of patients. The intensity of change in expression and its significance varied among the subsets. Nrf2 expression was raised in these species against oxidative stress as the antioxidant defense mechanism pertaining to Keap1-Nrf2 pathway, but the adequacy of response needs to be understood in further studies. The expression of KIR2DL4 and KIR3DL1 varied among the patient and healthy controls and the expression of the latter was found to have a significant positive relationship with plasma Glutathione(reduced) concentration.
系统性红斑狼疮是一种自身免疫性疾病,其症状遍及所有器官系统。与男性相比,它更常见于女性(比例为 9:1)。氧化应激在系统性红斑狼疮和其他自身免疫性疾病的发病机制中起着重要作用。为了了解细胞特异性氧化应激与系统性红斑狼疮严重程度之间的关系,本研究对北印度人群中的系统性红斑狼疮患者的 T 和 NK 细胞内 ROS 积累进行了评估。同时,估计了这些细胞类型中的 Keap1 和 Nrf2 水平以评估抗氧化防御。还评估了杀伤免疫球蛋白受体(即 KIR2DL4 和 KIR3DL1)的表达与氧化应激之间的关系,因为这些受体对于 NK 细胞的功能和自身耐受至关重要。氧化应激与 T 和 NK 细胞亚群中的 Keap1 和 Nrf2 一起升高。患者 NK 细胞中 KIR2DL4 的表达升高,而 KIR3DL1 的表达降低。表达变化的强度及其意义在亚群之间有所不同。Nrf2 的表达在这些物种中升高,以应对氧化应激,因为与 Keap1-Nrf2 途径相关的抗氧化防御机制,但需要进一步研究了解反应的充分性。KIR2DL4 和 KIR3DL1 的表达在患者和健康对照组之间存在差异,并且发现后者的表达与血浆谷胱甘肽(还原型)浓度呈显著正相关。