Cristian Iperi , Álvaro Fernández-Ochoa , Jacques-Olivier Pers , Guillermo Barturen , Marta Alarcón-Riquelme , PRECISESADS Flow Cytometry Study Group, PRECISESADS Clinical Consortium, Rosa Quirantes-Piné , Isabel Borrás-Linares , Antonio Segura-Carretero , Divi Cornec , Anne Bordon , Christophe Jamin
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引用次数: 0
Abstract
Objective
To link changes in the B-cell transcriptome from systemic lupus erythematosus (SLE) patients with those in their macroenvironment, including cellular and fluidic components.
Methods
Analysis was performed on 363 patients and 508 controls, encompassing transcriptomics, metabolomics, and clinical data. B-cell and whole-blood transcriptomes were analysed using DESeq and GSEA. Plasma and urine metabolomics peak changes were quantified and annotated using Ceu Mass Mediator database. Common sources of variation were identified using MOFA integration analysis.
Results
Cellular macroenvironment was enriched in cytokines, stress responses, lipidic synthesis/mobility pathways and nucleotide degradation. B cells shared these pathways, except nucleotide degradation diverted to nucleotide salvage pathway, and distinct glycosylation, LPA receptors and Schlafen proteins.
Conclusions
B cells showed metabolic changes shared with their macroenvironment and unique changes directly or indirectly induced by IFN-α signalling. This study underscores the importance of understanding the interplay between B cells and their macroenvironment in SLE pathology.
目的将系统性红斑狼疮(SLE)患者B细胞转录组的变化与其大环境(包括细胞和体液成分)的变化联系起来:对363名患者和508名对照者进行了分析,包括转录组学、代谢组学和临床数据。使用 DESeq 和 GSEA 分析了 B 细胞和全血转录组。使用 Ceu Mass Mediator 数据库对血浆和尿液代谢组学峰值变化进行量化和注释。利用 MOFA 整合分析确定了共同的变异来源:结果:细胞大环境富含细胞因子、应激反应、脂质合成/移动途径和核苷酸降解。除核苷酸降解转入核苷酸挽救途径外,B细胞共享这些途径,并具有独特的糖基化、LPA受体和Schlafen蛋白:结论:B细胞表现出与其大环境相同的代谢变化,以及由IFN-α信号直接或间接诱导的独特变化。这项研究强调了了解 B 细胞及其大环境在系统性红斑狼疮病理学中的相互作用的重要性。
期刊介绍:
Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.