PDF(Pubmed)
Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：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，特别关注那些在疾病缓解期间持续存在的人。
方法：我们对来自一个明确定义的队列的外周血单核细胞（PBMC）进行了大量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名患者出现疾病耀斑，和15个健康对照。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，包括鉴定差异表达的基因和途径，以及蛋白质-蛋白质相互作用网络的构建。
结果：与活动性疾病状态相比，缓解期恢复了几个转录组特征，包括下调血浆和细胞周期特征，以及淋巴细胞的上调。然而,特异性先天免疫应答特征，例如干扰素（IFN）签名，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可以针对这些持续特征的药物类别，有可能预防疾病复发。
结论：我们的综合转录组学研究揭示了SLE在活跃和缓解状态下的基因表达特征。在缓解阶段持续存在的基因表达模块的发现可能会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。
方法：我们对来自一个明确定义的队列的外周血单核细胞（PBMC）进行了大量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名患者出现疾病耀斑，和15个健康对照。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，包括鉴定差异表达的基因和途径，以及蛋白质-蛋白质相互作用网络的构建。
结果：与活动性疾病状态相比，缓解期恢复了几个转录组特征，包括下调血浆和细胞周期特征，以及淋巴细胞的上调。然而,特异性先天免疫应答特征，例如干扰素（IFN）签名，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可以针对这些持续特征的药物类别，有可能预防疾病复发。
结论：我们的综合转录组学研究揭示了SLE在活跃和缓解状态下的基因表达特征。在缓解阶段持续存在的基因表达模块的发现可能会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。
