Pahwa Roma, Kumar Uma, Das Nibhriti
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
Mol Cell Biochem. 2016 Mar;414(1-2):85-94. doi: 10.1007/s11010-016-2661-x. Epub 2016 Feb 23.
Studies have suggested that abnormal expression of complement regulatory proteins and cytokines contribute significantly to the path-physiology of rheumatoid arthritis. In this context, Decay accelerating factor (DAF) a complement regulatory protein is gaining increased attention. With the notion that immune effecter mechanisms are all interlinked and circulating peripheral blood mononuclear cells (PBMCs) should have a role in a systemic disease like rheumatoid arthritis, we studied the modulation and significance of PBMC-DAF and cytokines in RA. Seventy-five RA patients and 75 healthy controls were recruited. Expression of DAF and cytokines (IFN-γ, IL-17A and IL-10) in the PBMCs of patients and controls was determined. Correlations among DAF, cytokines, and disease activity were evaluated by standard statistical methods. The effect of IFN-γ, IL-17A, and IL-10 on the expression of DAF in patients and controls was studied in vitro. Expression of PBMC-DAF declined in patients both at mRNA and surface level and correlated negatively with the disease activity. Expression of IFN-γ also declined in patients but correlated positively with DAF and negatively with disease activity. Expression of IL-17A and IL-10 was higher in patients. The levels correlated positively with disease activity and negatively with DAF both in patients and controls. In vitro studies indicated that IFN-γ up-regulated DAF expression in PBMCs, whereas IL-17A and IL-10 had negative effect on the same. The decline in the PBMC-DAF is a contributing factor in manifestations of RA. Cytokine environment contributes to this decline. These findings brought novel insights into the complement-cytokine axis in the path-physiology of RA.
研究表明，补体调节蛋白和细胞因子的异常表达在类风湿性关节炎的病理生理学中起重要作用。在此背景下，补体调节蛋白衰变加速因子（DAF）越来越受到关注。鉴于免疫效应机制相互关联，且循环外周血单核细胞（PBMCs）在类风湿性关节炎等全身性疾病中应发挥作用，我们研究了类风湿性关节炎中PBMC-DAF和细胞因子的调节作用及意义。招募了75例类风湿性关节炎患者和75名健康对照。测定患者和对照PBMCs中DAF和细胞因子（IFN-γ、IL-17A和IL-10）的表达。通过标准统计方法评估DAF、细胞因子与疾病活动之间的相关性。在体外研究了IFN-γ、IL-17A和IL-10对患者和对照中DAF表达的影响。患者PBMC-DAF在mRNA和表面水平均下降，且与疾病活动呈负相关。患者中IFN-γ表达也下降，但与DAF呈正相关，与疾病活动呈负相关。患者中IL-17A和IL-10表达较高。患者和对照中其水平均与疾病活动呈正相关，与DAF呈负相关。体外研究表明，IFN-γ上调PBMCs中DAF表达，而IL-17A和IL-10对其有负面影响。PBMC-DAF下降是类风湿性关节炎表现的一个促成因素。细胞因子环境导致了这种下降。这些发现为类风湿性关节炎病理生理学中的补体-细胞因子轴带来了新的见解。
