期刊
CELL
卷 185, 期 18, 页码 3375-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2022.07.021
关键词
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资金
- Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
- Ministry of Education, Culture, Sports
- Japan Agency for Medical Research and Development (AMED) [JP21tm0424221, JP21zf0127004]
- Practical Research Project for Rare/Intractable Diseases from Japan AMED
- Distinguished Young Scholar of Provincial Natural Science Foundation of Anhui [1808085J08]
- National Research Foundation of Korea - Ministry of Education [NRF-2021R1A6A1A03038899]
This study conducted a large-scale transcriptome analysis to understand the dysregulated gene expression patterns in systemic lupus erythematosus (SLE). The researchers identified cell-type-specific transcriptomic signatures associated with disease establishment and exacerbation. The study suggested the clinical value of disease-activity signatures in predicting organ involvement and therapeutic responses.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple immune cells. To elucidate SLE pathogenesis, it is essential to understand the dysregulated gene expression pattern linked to various clinical statuses with a high cellular resolution. Here, we conducted a large-scale transcriptome study with 6,386 RNA sequencing data covering 27 immune cell types from 136 SLE and 89 healthy donors. We pro-filed two distinct cell-type-specific transcriptomic signatures: disease-state and disease-activity signatures, reflecting disease establishment and exacerbation, respectively. We then identified candidate biological pro-cesses unique to each signature. This study suggested the clinical value of disease-activity signatures, which were associated with organ involvement and therapeutic responses. However, disease-activity signatures were less enriched around SLE risk variants than disease-state signatures, suggesting that current genetic studies may not well capture clinically vital biology. Together, we identified comprehensive gene signatures of SLE, which will provide essential foundations for future genomic and genetic studies.
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