a Department of Rheumatology , Juntendo University School of Medicine , Tokyo , Japan.
b Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine , Chiba , Japan.
Autoimmunity. 2017 Jun;50(4):241-246. doi: 10.1080/08916934.2017.1329422. Epub 2017 May 27.
We previously reported that autoantibodies against the proliferating cell nuclear antigen protein (PCNA)-binding protein chromatin assembly factor-1 (CAF-1) are specifically found in patients with systemic lupus erythematosus (SLE). PCNA and its complex constituents elicit autoimmune responses in patients with SLE, suggesting that autoantibody diversification likely occurs owing to epitope spreading. Therefore, we sought to clarify whether patients with SLE exhibit an autoimmune response to Ribonuclease H2 (RNase H2), another PCNA-binding protein that regulates cell division. As results, RNase H2 autoantibodies were detected in the sera of 33.9% (19/56) of SLE patients, which was significantly higher than that observed in sera from other patients with systemic autoimmune diseases (polymyositis/dermatomyositis, systemic sclerosis, Sjogren's syndrome, mixed connective tissue disease and rheumatoid arthritis) and healthy controls. Regression analysis also showed that serum anti-RNase H2 levels were strongly correlated to that of CAF-1 in SLE patients. Our data support the use of RNase H2 autoantibodies as a serum biomarker for SLE diagnosis. Moreover, the strong correlation observed between RNase H2 and CAF-1 suggests that intermolecular epitope spreading may play a critical role in autoantibody production and diversification in SLE.
我们之前报道称,针对增殖细胞核抗原蛋白(PCNA)结合蛋白染色质组装因子-1(CAF-1)的自身抗体特异性存在于系统性红斑狼疮(SLE)患者中。PCNA 及其复合物成分在 SLE 患者中引发自身免疫反应,表明自身抗体多样化可能是由于表位扩展所致。因此,我们试图阐明 SLE 患者是否对另一种 PCNA 结合蛋白核糖核酸酶 H2(RNase H2)产生自身免疫反应,该蛋白调节细胞分裂。结果表明,在 33.9%(19/56)的 SLE 患者血清中检测到 RNase H2 自身抗体,明显高于其他系统性自身免疫性疾病(多发性肌炎/皮肌炎、系统性硬皮病、干燥综合征、混合性结缔组织病和类风湿关节炎)和健康对照组患者的血清中观察到的自身抗体。回归分析还表明,SLE 患者血清抗-RNase H2 水平与 CAF-1 水平呈强相关。我们的数据支持将 RNase H2 自身抗体用作 SLE 诊断的血清生物标志物。此外,RNase H2 和 CAF-1 之间观察到的强相关性表明,分子间表位扩展可能在 SLE 中的自身抗体产生和多样化中发挥关键作用。