Department of Rheumatology and Immunology, First Affiliated Hospital, China Medical University, Shenyang, 110001, People's Republic of China.
Department of 1st Cancer Institute, First Affiliated Hospital, China Medical University, Shenyang, 110001, People's Republic of China.
Clin Exp Med. 2017 Nov;17(4):459-465. doi: 10.1007/s10238-016-0448-8. Epub 2016 Dec 30.
DNase1l3 is an endonuclease to degrade the chromatin of apoptotic or necrotic cells. Serum DNase1l3 may fulfill the function of clearance of chromatin released into the circulation by dying cells, which can trigger autoimmune responses. To date, it remains unclear whether serum DNase1l3 level associates with the pathogenesis of autoimmune diseases. Sixty-eight patients with dermatomyositis/polymyositis (DM/PM, n = 30), systemic lupus erythematosus (SLE, n = 20) and rheumatoid arthritis (RA, n = 18), as well as 26 healthy blood donors were enrolled in the present study. Serum levels of DNase1l3 were quantified by enzyme-linked immunosorbent assay. DNASE1L3 activity in serum was estimated by the capability of serum to digest nucleosomal DNA. Clinical, biochemical, serological and other markers of disease activity (CRP, ESR, C3, C4, anti-Jo-1 and anti-dsDNA, etc.) were measured by standard laboratory procedure. We found a decrease in DNase1l3 level in the DM/PM and SLE patients, resulting in the reduction in serum activity to digest nucleosome DNA. In contrast, the level and activity of DNase1l3 remained unchanged in the RA patients. The DNase1l3 level was relatively lower in the DM/PM patients with anti-Jo-1 antibody and interstitial lung disease, and in the SLE patients with SLE disease activity index higher than 6, renal involvement and anti-dsDNA antibody. DNase1l3 level negatively correlated with CRP and IgG in the PM/DM patients and correlated with ESR in the SLE patients. We found a significant reduction in serum DNase1l3 level in DM/PM and SLE, which may associate with clinic features and disease activity.
DNase1l3 是一种内切核酸酶，可降解凋亡或坏死细胞的染色质。血清 DNase1l3 可能具有清除死亡细胞释放到循环中的染色质的功能，这可能会引发自身免疫反应。迄今为止，血清 DNase1l3 水平是否与自身免疫性疾病的发病机制相关仍不清楚。本研究纳入了 68 例皮肌炎/多发性肌炎（DM/PM，n=30）、系统性红斑狼疮（SLE，n=20）和类风湿关节炎（RA，n=18）患者以及 26 名健康献血者。采用酶联免疫吸附试验检测血清 DNase1l3 水平，通过血清消化核小体 DNA 的能力来估计血清中 DNASE1L3 的活性。采用标准实验室程序检测疾病活动的临床、生化、血清学和其他标志物（CRP、ESR、C3、C4、抗 Jo-1 和抗 dsDNA 等）。我们发现 DM/PM 和 SLE 患者的 DNase1l3 水平降低，导致血清消化核小体 DNA 的活性降低。相比之下，RA 患者的 DNase1l3 水平和活性保持不变。抗 Jo-1 抗体和间质性肺病的 DM/PM 患者以及疾病活动指数高于 6、肾脏受累和抗 dsDNA 抗体的 SLE 患者的 DNase1l3 水平相对较低。DNase1l3 水平与 PM/DM 患者的 CRP 和 IgG 呈负相关，与 SLE 患者的 ESR 呈正相关。我们发现 DM/PM 和 SLE 患者血清 DNase1l3 水平显著降低，这可能与临床特征和疾病活动有关。
