引用

线粒体为细胞提供能量并调节细胞凋亡。与其他哺乳动物细胞器不同，线粒体是由二元裂变形成的，不能由细胞直接产生。它们含有大量的紧凑环状基因组的副本，编码RNA分子和参与线粒体氧化磷酸化的蛋白质。然而，线粒体DNA (mtDNA)激活先天免疫系统，如果存在于细胞质或细胞外环境，它也是系统性红斑狼疮(SLE)循环自身抗体的目标。然而，目前尚不清楚SLE患者自身抗体是否也能识别线粒体RNA。在本研究中，我们评估了SLE中靶向线粒体RNA (AmtRNA)的自身抗体的存在。我们在小鼠SLE诱导模型中定量测定了AmtRNA。在SLE患者和健康志愿者中也检测到了AmtRNA。在我们诱导的小鼠SLE模型和人SLE模型中都测量了AmtRNA滴度，并进行了生物统计学分析，以确定AmtRNA的存在和/或水平是否与SLE患者表现出的临床特征相关。与健康对照组(n = 30)相比，SLE患者(n = 86) AmtRNA的IgG和IgM类均增加(p分别< 0.0001和p = 0.0493)。 AmtRNA IgG levels correlated with anti-mtDNA-IgG titers (rs = 0.54, p < 0.0001) as well as with both IgG and IgM against -2-glycoprotein I (anti-2GPI; rs = 0.22, p = 0.05), and AmtRNA-IgG antibodies were present at higher levels when patients were positive for autoantibodies to double-stranded-genomic DNA (p < 0.0001). AmtRNA-IgG were able to specifically discriminate SLE patients from healthy controls, and were negatively associated with plaque formation (p = 0.04) and lupus nephritis (p = 0.03). Conversely, AmtRNA-IgM titers correlated with those of anti-2GPI-IgM (rs = 0.48, p < 0.0001). AmtRNA-IgM were higher when patients were positive for anticardiolipin antibodies (aCL-IgG: p = 0.01; aCL-IgM: p = 0.002), but AmtRNA-IgM were not associated with any of the clinical manifestations assessed. These findings identify mtRNA as a novel mitochondrial antigen target in SLE, and support the concept that mitochondria may provide an important source of circulating autoantigens in SLE.