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Article Abstract

Autoimmune diseases (AIDs) constitute a group of disorders where the immune system mistakenly attacks the body's tissues. The pathogenesis of AIDs involve a breakdown in immune tolerance, culminating in an immune response that targets autoantigens. In adaptive immunity, secondary rearrangement of T cell receptors (TCRs) and B cell receptors (BCRs) involves sequential V(D)J recombination events during lymphocyte development. Imperfect receptor editing during this process can generate autoreactive clones, thereby contributing to the pathogenesis of AIDs. Emerging evidence implicates secondary V(D)J recombination in TCR and BCR genes as a pathogenic driver in multiple AIDs. The detection of secondary rearrangements, along with targeted therapeutic interventions (e.g. anti-CD40L, IL6), offers novel avenues for the early prediction and diagnosis of these diseases. This article provides a comprehensive overview of the current research on the role of TCR/BCR secondary rearrangements in AIDs, elucidating their mechanisms of action to enhance our understanding of the pathogenesis, diagnosis, and treatment of autoimmune disorders.

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http://dx.doi.org/10.1080/08820139.2025.2556781DOI Listing

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