Unveiling the Unique Immunological Landscape of Childhood-Onset Lupus through Single-Cell Transcriptomics 4768

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Abstract Description Childhood-onset systemic lupus erythematosus (cSLE) is clinically more severe than adult-onset SLE (aSLE), with increased disease activity and organ involvement. The immunological differences between cSLE and aSLE are poorly understood, limiting age-specific therapy development. To bridge this gap, we conducted a single-cell RNA sequencing (scRNA-seq) study on peripheral blood mononuclear cells (PBMCs) collected from sixteen childhood and four adult SLE patients from a longitudinal cohort established at Seoul National University Hospital. Our analysis identified cSLE-specific immune cell clusters, particularly within monocyte populations, marked by the upregulation of interferon-stimulated genes (ISGs) such as IFI27, IFI44L, and ISG15. Sub-clustering of monocytes and B cells revealed transcriptional signatures unique to cSLE, including enhanced CXCR4 expression in B cells, contributing to increased migration and pathogenic potential. These findings provide molecular evidence linking dysregulated Type I interferon signaling with the greater disease severity observed in cSLE. This study is among the first to systematically dissect the immune architecture of cSLE at single-cell resolution, highlighting the role of interferon pathways in cSLE pathogenesis. Our findings pave the way for developing age-specific targeted therapies aimed at modulating aberrant interferon responses in cSLE, ultimately improving outcomes for pediatric patients with this severe autoimmune disease. Topic Categories Basic Autoimmunity (BA)

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