Multiplexed scRNA-seq reveals the cellular and genetic correlates of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and cell states associated with SLE remains incomplete. We profiled over 1.2 million PBMCs (162 cases, 99 controls) with multiplexed single-cell RNA-seq (mux-seq). Cases exhibited prominent expression of type-1 interferon-stimulated genes (ISG) in monocytes, reduction of naïve CD4+ T cells that correlated with monocyte ISG expression, and expansion of repertoire-restricted cytotoxic GZMH+ CD8+ T cells. Cell-type-specific expression features accurately predicted case-control status and stratified patients into two molecular subtypes. We integrated dense genotyping data, mapping cell-type-specific cis-eQTLs and linked known and novel SLE-associated variants to cell-type-specific gene expression. These results demonstrate mux-seq as a systematic approach to characterize cellular composition, identify transcriptional signatures, and annotate genetic variants associated with SLE. Examination of 1.2 million PBMCs in 162 SLE donors and 99 healthy individuals to find cellular and genetic correlates of SLE. **The raw data and processed data will be made available in dbGaP (https://www.ncbi.nlm.nih.gov/gap/) through controlled access due to patient privacy concerns**