Papanikolaou Sofia, Kosmara Despoina, Stathopoulou Chrysoula, Sidiropoulos Prodromos, Konstantopoulos Dimitrios, Bertsias George
Rheumatology and Clinical Immunology, University of Crete Medical School and University Hospital of Heraklion, Heraklion, Greece.
Infections and Immunity, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Greece.
Mediterr J Rheumatol. 2022 Mar 31;33(1):94-98. doi: 10.31138/mjr.33.1.94. eCollection 2022 Mar.
A remarkable, yet poorly explained feature of Systemic Lupus Erythematosus (SLE) is the propensity to flare following a preceding period of disease inactivity. The clinical burden of lupus flares is substantial since they often tend to involve multiple or major organs, and carry a near two-fold increased risk for accrual of irreversible organ damage. The cellular and molecular mechanisms underlying the progression of SLE from inactive to active state remain ill-defined. Application of novel sequencing technologies together with cellular immunology assays, have illustrated the important role of multiple types of both innate and adaptive cells and associated pathways. We have previously described significant differences in the blood transcriptome of SLE patients at active versus inactive disease, and we have also defined genome regions (domains) with co-ordinated expression of genes implicated in the disease. In the present study, we aim to decipher the cellular and molecular basis of SLE exacerbations by utilising novel single-cell sequencing approaches, which allow us to characterise the transcriptional and epigenetic landscapes of thousands of cells in the peripheral blood of patients. The significance of the study lies in the detailed characterisation of the molecular and regulatory program of immune cell subpopulations that underlie progression from inactive to active SLE. Accordingly, our results may be exploited to identify biomarkers for disease monitoring and novel therapeutic targets.
系统性红斑狼疮（SLE）一个显著却又难以解释的特征是，在疾病静止期之后易于复发。狼疮复发带来的临床负担很重，因为它们往往累及多个或主要器官，且累积不可逆器官损伤的风险增加近两倍。SLE从静止状态发展到活动状态的细胞和分子机制仍不清楚。新型测序技术与细胞免疫学检测方法的应用，已阐明了多种先天和适应性细胞及相关通路的重要作用。我们之前描述了SLE患者活动期与静止期血液转录组的显著差异，并且还确定了与疾病相关的基因协同表达的基因组区域（结构域）。在本研究中，我们旨在通过利用新型单细胞测序方法来解读SLE病情加重的细胞和分子基础，该方法使我们能够描绘患者外周血中数千个细胞的转录和表观遗传图谱。该研究的意义在于详细描绘了免疫细胞亚群的分子和调控程序，这些程序是SLE从静止期发展到活动期的基础。因此，我们的研究结果可用于识别疾病监测的生物标志物和新的治疗靶点。
