Frontiers in immunology · 2026
Single-cell mass cytometry cartography highlights systemic lupus erythematosus and Sjögren's disease immune differences.
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Szelinski Franziska, Stefanski Ana-Luisa, Wiedemann Annika, Rincon-Arevalo Hector, Schrezenmeier Eva, Alexander Tobias, Dang Van Duc, Frei Andreas, Lino Andreia C, Dörner Thomas
Аннотация
OBJECTIVES: 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).
METHODS: 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.
RESULTS: 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 CD19low 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 CD226hi 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.
CONCLUSION: 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.
METHODS: 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.
RESULTS: 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 CD19low 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 CD226hi 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.
CONCLUSION: 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.