Sjögren's disease & overlap diseases

Multimodal Single‐Cell Sequencing of B Cells in Primary Sjögren's Syndrome

Arthritis RheumatolPublished Mechanistic study

Authors' conclusion

We describe heterogeneity and molecular characteristics in B cells from patients with pSS, providing clues to intrinsic differences in B cells that affect the phenotype and outcome and allowing stratification of patients with pSS at improved resolution.

Study context

Population
Peripheral blood B cells (over 230,000) from patients with pSS and healthy controlsOver 230,000 B cells
Participants
6 / 8 / 10 / 4
Comparison
pSS subgroups stratified by SSA/SSB antibodies vs healthy controls
  • SSA-n = 6
  • SSA+n = 8
  • SSA/SSB+n = 10
  • Healthy controlsn = 4reference
Methodological detailssingle-cell RNA sequencing, single-cell variable, diversity, and joining (VDJ) sequencing
  • Single-cell RNA sequencing
  • Single-cell VDJ sequencing

Main finding

As reported in the abstract

  • SSA/SSB+ patients had the highest proportion of naïve and lowest proportion of memory B cells
  • SSA/SSB+ patients had the highest up-regulation of interferon-induced genes across all B cell subtypes
  • IGHV1-69 and IGHV4-30-4 more often used in all pSS subgroups vs controls
  • Memory B cells from SSA/SSB+ patients had a higher proportion of unmutated VDJ transcripts vs other pSS groups and controls, indicating altered somatic hypermutation
  • Heterogeneous clonotype pools with little overlap in CDR3 sequences vs previous studies
  • Joint single-cell RNA sequencing (scRNA-seq) and scVDJ-seq analysis allowed unsupervised stratification of pSS and identified novel parameters correlated to disease manifestations and antibody status

Original publication

Multimodal Single‐Cell Sequencing of B Cells in Primary Sjögren's Syndrome. Arthritis Rheumatol. Published 18 December 2023. doi:10.1002/art.42683

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