• Yixi Li, Fangfang Ge, Chengxun Liu, Wenjun Pu, Wei Lv, Zhipeng Zeng, Lianghong Yin, Dongzhou Liu, Yasong Li, Donge Tang, Peng Han, and Yong Dai.
• 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.
• Transl Res. 2024 Nov 1; 273: 115126115-126.

AbstractExtrachromosomal 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.Copyright © 2024 Elsevier Inc. All rights reserved.

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