Bioinformatics, AMPEL BioSolutions, Charlottesville, Virginia, USA
Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA.
Lupus Sci Med. 2023 Jan;10(1). doi: 10.1136/lupus-2022-000861.
To character the molecular landscape of patients with type 1 and type 2 SLE by analysing gene expression profiles from peripheral blood.
Full transcriptomic RNA sequencing was carried out on whole blood samples from 18 subjects with SLE selected by the presence of manifestations typical of type 1 and type 2 SLE. The top 5000 row variance genes were analysed by Multiscale Embedded Gene Co-expression Network Analysis to generate gene co-expression modules that were functionally annotated and correlated with various demographic traits, clinical features and laboratory measures.
Expression of specific gene co-expression modules correlated with individual features of type 1 and type 2 SLE and also effectively segregated samples from patients with type 1 SLE from those with type 2 SLE. Unique type 1 SLE enrichment included interferon, monocytes, T cells, cell cycle and neurotransmitter pathways, whereas unique type 2 SLE enrichment included B cells and metabolic and neuromuscular pathways. Gene co-expression modules of patients with type 2 SLE were identified in subsets of previously reported patients with inactive SLE and idiopathic fibromyalgia (FM) and also identified subsets of patients with active SLE with a greater frequency of severe fatigue.
Gene co-expression analysis successfully identified unique transcriptional patterns that segregate type 1 SLE from type 2 SLE and further identified type 2 molecular features in patients with inactive SLE or FM and with active SLE with severe fatigue.
通过分析外周血基因表达谱，描述 1 型和 2 型系统性红斑狼疮（SLE）患者的分子特征。
选择有 1 型和 2 型 SLE 典型表现的 18 例 SLE 患者的全血样本进行全转录组 RNA 测序。采用多尺度嵌入式基因共表达网络分析对前 5000 个差异基因进行分析，生成基因共表达模块，并对其进行功能注释，与各种人口统计学特征、临床特征和实验室指标进行相关性分析。
特定基因共表达模块的表达与 1 型和 2 型 SLE 的个体特征相关，并且能够有效区分 1 型和 2 型 SLE 患者的样本。1 型 SLE 独特的富集途径包括干扰素、单核细胞、T 细胞、细胞周期和神经递质途径，而 2 型 SLE 独特的富集途径包括 B 细胞以及代谢和神经肌肉途径。在先前报道的无活性 SLE 和特发性纤维肌痛（FM）患者亚组中鉴定出了 2 型 SLE 的基因共表达模块，在有严重疲劳的活动性 SLE 患者亚组中也鉴定出了这些模块。
基因共表达分析成功地识别了能够区分 1 型 SLE 和 2 型 SLE 的独特转录模式，并进一步在无活性 SLE 或 FM 患者以及有严重疲劳的活动性 SLE 患者中鉴定出了 2 型分子特征。
