{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:56:25Z","timestamp":1781585785379,"version":"3.54.5"},"reference-count":144,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Autoimmune diseases result from a breakdown of immune tolerance, driving the aberrant activation and clonal expansion of self-reactive T and B cells. Progress has been limited by the inability to link clonal identity to functional states at single-cell resolution. Single-cell T- and B-cell receptor sequencing (scTCR\/BCR-seq) now bridges this gap by simultaneously recovering paired TCR (\u03b1\/\u03b2) and BCR (heavy\/light) chains and gene-expression profiles, enabling direct coupling of clonotypes to cellular function and tissue trafficking. This shift from population-level averaging to clonal-resolution analysis, particularly when integrated with multi-omics, has yielded substantial insights. Mechanistically, scTCR\/BCR-seq identifies tissue-homing, putatively pathogenic clones and resolves somatic hypermutation, class-switch recombination, and T-B cell interaction networks, thereby delineating the clonal basis of disease heterogeneity. Clinically, it enables tracking of clonal dynamics to inform prognosis and to predict responses to therapies such as anti-CD20 or BAFF-targeted agents. For therapeutic development, reconstructing autoantibodies from BCR clones and mapping epitopes through TCR analysis provide a foundation for antigen-specific tolerance strategies. This review synthesizes scTCR\/BCR-seq methodologies and systematically charts these advances and discusses current challenges and future directions toward precision subtyping, biomarker development, and novel immunotherapies in autoimmune disease.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1827384","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:29:23Z","timestamp":1781584163000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding autoimmune disease with single-cell immune repertoire and transcriptome sequencing: mechanisms and therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Shuqing","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences, Special Key Laboratory of Gene Detection and Therapy of Guizhou Province, Zunyi Medical University","place":["Zunyi, China"]},{"name":"Department of Immunology, Key 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