Distinct transcriptome architectures underlying lupus establishment and exacerbation
Distinct transcriptome architectures underlying lupus establishment and exacerbation
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DOI：
10.1016/j.cell.2022.07.021
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发表时间：
2022-09-01
期刊：
影响因子：
64.5
通讯作者：
Fujio, Keishi
中科院分区：
文献类型：
--
作者：
Nakano, Masahiro;Ota, Mineto;Fujio, Keishi
系统性红斑狼疮（SLE）是一种复杂的自身免疫性疾病，涉及多个免疫细胞。为了阐明SLE的发病机制，有必要以高细胞分辨率了解与各种临床状态相关的失调基因表达模式。在这里，我们进行了一项大规模的转录组研究，包括来自136名SLE患者和89名健康供者的27种免疫细胞类型的6386个RNA测序数据。我们提出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，分别反映疾病的建立和恶化。然后，我们确定了每个特征独特的候选生物过程。本研究提示疾病活动特征的临床价值，这些特征与器官受累和治疗反应有关。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，这表明目前的遗传研究可能无法很好地捕获临床重要生物学。我们共同确定了SLE的全面基因特征，这将为未来的基因组和遗传学研究提供必要的基础。
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.