Multi-modal single cell sequencing of B cells in primary Sjögren’s Syndrome

Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration in the salivary and lacrimal glands, B cell activation, SSA/SSB autoantibodies and an increased risk of B cell lymphoma. By generating sorted B cell single-cell gene expression and BCR libraries from 24 pSS patients stratified by SSA/SSB antibodies and four healthy controls, we defined 16 B cell subtypes. Interferon response genes were upregulated in pSS across all B cell subtypes, with the highest levels in pSS with both SSAB antibodies. The SSAB group showed a higher proportion of naïve B cells and lower proportion of memory B cells compared with controls. Memory B cells from SSAB patients were not class switched and expressed unmutated VDJ sequences. IGHV1-69 repertoire frequencies were higher in pSS patients than controls and 1287 clonotypes were unique for pSS. The present study describes molecular differences which may enable stratification of pSS patients at improved resolution. B cells from the peripheral blood from 24 patients with primary Sjögren's syndrome (pSS), from three patient groups based on auto-antibody stratification (SSA-: pSS patients where auto-antibodies to SSA or SSB were not detected (n = 6). SSA+: pSS patients where SSA but not SSB auto-antibodies were detected (n = 8). SSAB: pSS patients where SSA and SSB auto-antibodies were detected (n = 10)), and B cells from the peripheral blood of four healthy controls. >>>Submitter states: Raw data are not available due to patient privacy concerns<<<