Lupus & antiphospholipid syndrome

Multimodal repertoire analysis unveils B cell biology in immune-mediated diseases

Ann Rheum DisPublished Mechanistic study

Authors' conclusion

Our multimodal repertoire analysis enabled us the system-level understanding of B cell abnormality in diseases.

Study context

Population
Donors with immune-mediated diseases and healthy donors; five sorted B cell subsetsImmune-mediated diseases (IMDs) and health
Participants
595 donors
Methodological detailsmultimodal B cell receptor repertoire analysis, RNA sequencing of sorted B cell subsets
  • Multimodal B cell receptor repertoire analysis
  • RNA sequencing of sorted B cell subsets

Main finding

As reported in the abstract

  • CDR-H3 length among naïve B cells shortened in autoimmune diseases
  • Strong negative correlation between interferon signature strength and CDR-H3 length in naïve B cells
  • VDJ gene usage skewed especially in plasmablasts and unswitched-memory B cells of patients with systemic lupus erythematosus (SLE)
  • Skewing score correlated positively with peripheral helper T cell transcriptomic signatures and negatively with somatic hypermutation in plasmablasts
  • High IGHV4-34 usage with 9G4 idiotypes in unswitched-memory B cells, with prominent positive correlation with SLE disease activity
  • Gene usage skewing in unswitched-memory B cells ameliorated after belimumab treatment

Original publication

Multimodal repertoire analysis unveils B cell biology in immune-mediated diseases. Ann Rheum Dis. Published 19 July 2023. doi:10.1136/ard-2023-224421

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