Single-cell mass cytometry cartography highlights systemic lupus erythematosus and Sjögren’s disease immune differences
- 1Deutsches Rheuma-Forschungszentrum, a Leibniz Institute , ,
- 2Roche Innovation Center Basel , ,
Abstract
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 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.
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.
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BibTeX
@article{szelinski2026singlecell,
title = {{Single-cell mass cytometry cartography highlights systemic lupus erythematosus and Sjögren’s disease immune differences}},
author = {Franziska Szelinski and Ana-Luisa Stefanski and Annika Wiedemann and Hector Rincon-Arevalo and Eva Schrezenmeier and Tobias Alexander and Van Duc Dang and Andreas Frei and Andreia C. Lino and Thomas Dörner},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1834700},
url = {https://europepmc.org/article/PMC/PMC13669203},
note = {CC BY},
}
RIS
TY - JOUR
TI - Single-cell mass cytometry cartography highlights systemic lupus erythematosus and Sjögren’s disease immune differences
AU - Franziska Szelinski
AU - Ana-Luisa Stefanski
AU - Annika Wiedemann
AU - Hector Rincon-Arevalo
AU - Eva Schrezenmeier
AU - Tobias Alexander
AU - Van Duc Dang
AU - Andreas Frei
AU - Andreia C. Lino
AU - Thomas Dörner
PY - 2026
DA - 2026/10/01
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1834700
UR - https://europepmc.org/article/PMC/PMC13669203
AB - 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 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. 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.
SN - 1664-3224
ER -