Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease with extreme heterogeneity, marked clinically by multi-systemic inflammatory involvement. However, the molecular mechanism of breakdown of self-tolerance is still unclear. T cell/B cell-mediated immune disorders may play a vital role in the pathogenesis of SLE.
Methods: In this context, we used a combination of multiplex-PCR, Illumina sequencing and IMGT/HighV-QUEST for a standardised analysis of the T cell receptor β-chain (TCRβ) and B cell receptor H-chain (BCR-H) repertoire of peripheral blood mononuclear cells in SLE patients compared with healthy volunteers.
Results: The results showed that there was an obvious reduction in BCR-H repertoire diversity and BCR-H CDR3 length in SLE patients. Notably, the pre-selection BCR-H CDR3s in SLE patients also displayed abnormal shortening, which suggests that early events in bone marrow B cell development and repertoire generation were abnormal in SLE patients. However, there was no obvious change of T cell repertoire in SLE patients, including repertoire diversity and CDR3 length. In addition, there was skewed usage of V genes and CDR3 sequences in SLE patients, which might be the result of physiological responses to environmental antigens or pathogens.
Conclusions: In conclusion, our data revealed the specific changes of the TCR and BCR repertoires in SLE patients, which may provide new ideas for its prevention and treatment.
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