Multi-Omic Profiling Reveals Immune Cell Priming Signature Linked to Lupus Prognosis

Systemic lupus erythematosus (SLE) is a multiorgan disease with widespread immune dysregulation and significant unmet clinical need. Blood-based gene expression studies have advanced our understanding of SLE pathogenesis but may overlook critical tissue-specific mechanisms that drive disease heterogeneity and progression. We posited that integrated multidimensional profiling could reveal novel molecular patterns underlying distinct SLE pathologies.

Here, we integrated immune cell, protein, and transcriptome data sets with disease activity and damage indices across 87 patients with SLE to reveal three independent protein signatures corresponding to discrete organ pathologies and immune perturbations.

Alongside type I interferon and granulocyte pathways, our multidimensional analyses identified a previously uncharacterized immune cell priming protein signature that was enriched in patients with renal involvement and was indicative of elevated risk of six-year organ damage accrual. This minimally invasive signature outperformed conventional assessments and was only found in the serum proteomics data. Collectively, the protein signatures demonstrated a combined prevalence of 94%, reflecting their broad relevance to SLE.

Together, these results reveal parallel immune mechanisms in SLE and provide a framework to identify new therapeutic targets. Clinical and immune data are available for public exploration through the interactive SLE Immune Atlas.