Comprehensive Immune Repertoires of T Cell Receptor and B Cell Receptor Identify Key Immune Features Associated With Disease Activity of Systemic Lupus Erythematosus

We integrated immune repertoire sequencing (CD4+ and CD8+ T cell receptor [TCR], B cell receptor [BCR]) and transcriptional profiling to characterize the peripheral immune landscape in 32 active systemic lupus erythematosus (SLE) patients, 30 stable SLE patients, and 35 healthy donors. CD4+ and CD8+ TCR α- and β-chain repertoires in SLE patients showed lower diversity, reduced similarity, and more heterogeneous V-J usage, with CD8+ TCR profiles exhibiting relatively consistent stepwise changes across healthy, stable, and active groups. CD8+ T-cell transcriptomics revealed activity-associated upregulation of CD38, S100A11, IFITM3, and LAG3. In addition, BCR immunoglobulin heavy chain (IGH) repertoire analysis showed isotype-specific remodeling in SLE, characterized by contracted IgM/IgD repertoires, increased IgA isotype ratio and richness, and enhanced IgG diversity. Active SLE showed further increased IgG richness with rare-clone enrichment and higher IgM diversity. Among the TCR, BCR, and CD8+ T-cell transcriptomic features evaluated, IGH-derived metrics, particularly IgG- and IgA-associated features, showed apparent within-cohort discrimination between active and stable SLE. Genetic algorithm-based label-guided feature selection followed by hierarchical clustering revealed a multi-omics pattern associated with disease activity within the current cohort. Our study characterized peripheral immune repertoire and transcriptional alterations in SLE and highlighted their value for characterizing disease activity.