Nakano Masahiro, Ota Mineto, Takeshima Yusuke, Iwasaki Yukiko, Hatano Hiroaki, Nagafuchi Yasuo, Itamiya Takahiro, Maeda Junko, Yoshida Ryochi, Yamada Saeko, Nishiwaki Aya, Takahashi Haruka, Takahashi Hideyuki, Akutsu Yuko, Kusuda Takeshi, Suetsugu Hiroyuki, Liu Lu, Kim Kwangwoo, Yin Xianyong, Bang So-Young, Cui Yong, Lee Hye-Soon, Shoda Hirofumi, Zhang Xuejun, Bae Sang-Cheol, Terao Chikashi, Yamamoto Kazuhiko, Okamura Tomohisa, Ishigaki Kazuyoshi, Fujio Keishi
Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo 113-0033, Japan; Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo 113-0033, Japan; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, the University of Tokyo, Tokyo 113-0033, Japan.
Cell. 2022 Sep 1;185(18):3375-3389.e21. doi: 10.1016/j.cell.2022.07.021. Epub 2022 Aug 22.
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 profiled two distinct cell-type-specific transcriptomic signatures: disease-state and disease-activity signatures, reflecting disease establishment and exacerbation, respectively. We then identified candidate biological processes 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.
系统性红斑狼疮（SLE）是一种涉及多种免疫细胞的复杂自身免疫性疾病。为了阐明SLE的发病机制，有必要在高细胞分辨率下了解与各种临床状态相关的基因表达失调模式。在此，我们进行了一项大规模转录组研究，分析了来自136名SLE患者和89名健康供体的6386个RNA测序数据，涵盖27种免疫细胞类型。我们描绘了两种不同的细胞类型特异性转录组特征：疾病状态和疾病活动特征，分别反映疾病的发生和加重。然后，我们确定了每个特征所特有的候选生物学过程。这项研究表明了疾病活动特征的临床价值，其与器官受累和治疗反应相关。然而，与疾病状态特征相比，疾病活动特征在SLE风险变异周围的富集程度较低，这表明目前的基因研究可能无法很好地捕捉临床上至关重要的生物学信息。我们共同确定了SLE的综合基因特征，这将为未来的基因组和基因研究提供重要基础。
