scRNA+VDJ-seq in SLE: Insights into autoreactive T and B cell subsets, features, and therapeutic applications.

The adaptive autoimmune process in SLE is complex, and conventional techniques cannot resolve disease-associated T/B lymphocyte clones at a single-cell granularity. Single-cell RNA sequencing combined with single-cell V(D)J sequencing (scRNA+VDJ-seq) enables simultaneous profiling of cellular transcriptomes and TCR/BCR repertoires. This review highlights recent advances in scRNA+VDJ-seq in SLE and related autoimmune disorders, elucidating the link between receptor clonality, gene expression, and effector phenotypes. It delineates clonal expansion, biased V(D)J usage, and aberrant exhaustion in SLE, and compares T/B cell immune phenotypes across lupus nephritis, RA, pSS, and AS. The review also summarizes CD19 CAR-T and PD-1 agonist applications. Furthermore, it discusses AI integration with scRNA+VDJ-seq to analyze autoreactive T/B cells in SLE: from data integration to clinical translation, and assesses the clinical translational potential of this technology, offering novel targets and strategies for SLE diagnosis, personalized treatment, and prognosis.