Li Yixi, Ge Fangfang, Liu Chengxun, Pu Wenjun, Lv Wei, Zeng Zhipeng, Yin Lianghong, Liu Dongzhou, Li Yasong, Tang Donge, Han Peng, Dai Yong
Center for General Practice Medicine, Department of Rheumatology and Immunology, Zhejiang Provincial People' s Hospital (Affiliated People' s Hospital), Hangzhou Medical College, Hangzhou 310000, China; Guangdong Provincial Autoimmune Disease Precision Medicine Engineering Research Center, Shenzhen Autoimmune Disease Engineering Research Center, Shenzhen Geriatrics Clinical Research Center, Shenzhen People 's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 518020, China.
Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI Research, Qingdao 266555, China.
Transl Res. 2024 Nov;273:115-126. doi: 10.1016/j.trsl.2024.08.004. Epub 2024 Aug 20.
Extrachromosomal circular DNA (eccDNA) derived from linear chromosomes, are showed typical nucleosomal ladder pattern in agarose gel which as a known feature of apoptosis and demonstrated to be immunogenicity. In systemic lupus erythematosus (SLE) patients, elevated levels of cell-free DNA (cfDNA) can be found in either linear forms or circular forms, while circular ones are much less common and harder to detect. The molecular characteristics and function of circular forms in plasma SLE patients remains elusive. Herein, we characterized the hallmarks of plasma eccDNA in SLE patients, including the lower normalized number and GC content of eccDNA in SLE plasma than in the healthy, and SLE eccDNA number positively correlated with C3 and negatively with anti-dsDNA antibodies. The differential eccGenes (eccDNAs carrying the protein coding gene sequence) of SLE was significantly enriched in apoptosis-related pathways. The artificially synthesized eccDNA with sequences of the PRF1 exon region could promote transcriptional expression of PRF1, IFNA and IFIT3 and inhibit early-stage apoptosis. Plasma eccDNA can serve as a novel autoantigen in the pathogenesis of SLE.
源自线性染色体的染色体外环状DNA（eccDNA）在琼脂糖凝胶中呈现典型的核小体梯状模式，这是细胞凋亡的一个已知特征，并被证明具有免疫原性。在系统性红斑狼疮（SLE）患者中，可发现游离DNA（cfDNA）水平升高，其形式包括线性或环状，而环状形式则更为罕见且更难检测。SLE患者血浆中环状形式的分子特征和功能仍不清楚。在此，我们对SLE患者血浆eccDNA的特征进行了描述，包括SLE血浆中eccDNA的标准化数量和GC含量低于健康人，且SLE的eccDNA数量与C3呈正相关，与抗双链DNA抗体呈负相关。SLE的差异ecc基因（携带蛋白质编码基因序列的eccDNA）在凋亡相关途径中显著富集。人工合成的具有PRF1外显子区域序列的eccDNA可促进PRF1、IFNA和IFIT3的转录表达并抑制早期细胞凋亡。血浆eccDNA可作为SLE发病机制中的一种新型自身抗原。
