Single-cell mass cytometry cartography highlights systemic lupus erythematosus and Sjögren’s disease immune differences

Abstract

Autoimmune diseases such as primary Sjögren’s disease (pSjD) and systemic lupus erythematosus (SLE) share clinical and serological features, including type I interferon signatures, autoantibody formation, and chronic inflammation, but the underlying immunopathology is not the same. To support the development of targeted therapies, we aimed to systematically characterize disease-specific alterations in peripheral immune cell subsets of pSjD and SLE compared to healthy donors (HD). We analyzed peripheral blood mononuclear cells from 15 HD, 12 pSjD and 21 SLE patients by mass cytometry. We manually pre-gated viable CD19 + B cells, CD3 + T cells, and innate immune populations before performing high-dimensional, consensus clustering. We compared relative subset frequencies and marker expression, including costimulatory and inhibitory receptors, between the three cohorts. In the B cell compartment, we identified 13 clusters. SLE patients showed an relative expansion of plasmablasts and two double-negative (IgD − CD27 − ) B cell clusters, one CD21 − and one CD19 low with high IgA. Both had an activated phenotype with elevated CD38, CD86, and Ki-67. In SLE, the costimulatory molecules CD86 and CD226 were upregulated on memory and DN B cells. By contrast, B cell changes in pSjD were more modest. We found 12 T cells clusters. Both diseases had increased CD4 + PD-1 + ICOS + circulating T follicular helper-like cells, and pSjD showed expansion of CD8 + effector memory (Tem) and terminally differentiated (Temra) T cell subsets. Relative innate cell frequencies did not differ substantially between groups, however, intermediate CD226 hi monocytes were reduced in SLE but showed higher activation marker expression (CD86, HLA-DR). Network correlation analysis revealed higher immune‐cell connectivity in SLE compared to pSjD. SLE is characterized by B cell activation, plasmablast expansion, and costimulatory upregulation, while pSjD is mainly defined by alterations in the CD8 + T cell compartment. These disease‐specific immunologic signatures highlight distinct patterns in SLE and pSjD and generate hypotheses for future studies investigating targeted therapeutic approaches.