Deciphering the Molecular Mechanism of Flares in Patients with Systemic Lupus Erythematosus through Single-Cell Transcriptome Analysis of the Peripheral Blood

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.