Aggarwal Ashish, Sharma Aman, Bhatnagar Archana
Department of Biochemistry, Basic Medical Sciences Block, Panjab University, Chandigarh, India.
Clin Rheumatol. 2014 Aug;33(8):1067-78. doi: 10.1007/s10067-014-2641-z. Epub 2014 May 7.
Innate immunity has been widely accepted as one of the major cause for the alteration of immune system and progression of autoimmune diseases. Natural killer (NK) cells and natural killer T (NKT) cells have not been explored in clinical studies for their cytolytic components in association with rheumatoid arthritis (RA). The literature available for these potential candidates is controversial in terms of their protective or pathogenic role in disease severity of RA. Present study explained the role of NK and NKT cell populations and intracellular expression of caspases, perforin, granzymes A and B in the pathogenesis of RA in patients. DAS28 score was measured as the disease severity. Immunochemical parameters were studied by using monoclonal antibodies (mAbs) against different cell types in flow cytometry. Results indicated that that whatsoever is the change in percentage cell populations, ratio of NK and NKT cell populations always remained poised even in the disease state. Reactive oxygen species (ROS) levels were elevated with increased intracellular active caspase-3, perforin and granzyme expression in RA patients. Their elevated expressions were positively correlated with DAS28 suggesting the pathogenic role in RA. The expressions of pro-inflammatory cytokines were enhanced while the anti-inflammatory cytokine expressions were diminished in the patients. Present study may point towards futuristic therapeutic targets which can fascinate the pharmaceutical industries to selectively target these molecules in designing the therapeutic strategy of RA patients.
先天免疫已被广泛认为是免疫系统改变和自身免疫性疾病进展的主要原因之一。自然杀伤(NK)细胞和自然杀伤T(NKT)细胞在类风湿性关节炎(RA)相关的临床研究中尚未对其细胞溶解成分进行探索。关于这些潜在候选细胞在RA疾病严重程度中的保护或致病作用,现有文献存在争议。本研究解释了NK和NKT细胞群体以及半胱天冬酶、穿孔素、颗粒酶A和B的细胞内表达在RA患者发病机制中的作用。以DAS28评分作为疾病严重程度的指标。通过在流式细胞术中使用针对不同细胞类型的单克隆抗体(mAb)来研究免疫化学参数。结果表明,无论细胞群体百分比如何变化,即使在疾病状态下,NK和NKT细胞群体的比例始终保持平衡。RA患者中活性氧(ROS)水平升高,细胞内活性半胱天冬酶-3、穿孔素和颗粒酶表达增加。它们的升高表达与DAS28呈正相关,表明在RA中具有致病作用。患者体内促炎细胞因子的表达增强,而抗炎细胞因子的表达减少。本研究可能指向未来的治疗靶点,这可能会吸引制药行业在设计RA患者的治疗策略时选择性地靶向这些分子。