This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

中文翻译：

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揭示系统性红斑狼疮不同疾病状态下的转录组特征和失调途径

本研究旨在阐明系统性红斑狼疮 (SLE) 患者的转录组特征和失调通路，特别关注疾病缓解期间持续存在的转录组特征和失调通路。我们对一组明确的外周血单核细胞 (PBMC) 进行了批量 RNA 测序，该队列包括 26 名符合低狼疮疾病活动状态 (LLDAS) 标准的缓解患者、76 名经历疾病发作的患者和 15 名健康对照者。为了阐明与不同疾病状态相关的免疫特征变化，我们进行了广泛的分析，包括识别差异表达的基因和通路，以及蛋白质-蛋白质相互作用网络的构建。与活动性疾病状态相比，缓解期间恢复了一些转录组学特征，包括血浆和细胞周期特征的下调以及淋巴细胞的上调。然而，特定的先天免疫反应特征，例如干扰素 (IFN) 特征和参与染色质结构修饰的基因模块，在不同的疾病状态下持续存在。药物再利用分析揭示了某些药物类别可以针对这些持久特征，从而有可能预防疾病复发。我们全面的转录组研究揭示了系统性红斑狼疮在活动期和缓解期的基因表达特征。在缓解阶段持续存在的基因表达模块的发现可能有助于揭示这些患者易复发的潜在机制，为他们的治疗提供有价值的见解。