Blerina Aliraj, MSc: No financial relationships to disclose
Introduction/Rationale: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by systemic chronic inflammation that can lead to heterogeneous clinical manifestations, from mild cutaneous disease to multi-organ damage and failure. Understanding how immune cell composition, their activation status, and metabolic changes contribute to disease is important to identify new biomarkers and therapeutic targets.
Methods: In this study, we combined spectral flow cytometry and CITE-Seq to profile immune cell subsets and metabolic changes at the single-cell level. Peripheral white blood cells from SLE patients, psoriatic arthritis (PsA) patients, and healthy donors were analyzed using a 50-marker panel that evaluated immune subsets, activation and exhaustion markers, including metabolic dependencies by using SCENITH. The same antibody panel was used in CITE-Seq to validate flow cytometric findings and explore additional metabolic and inflammation pathways. High-dimensional computational analysis was used to identify immune subpopulations with specific metabolic signatures that distinguished SLE from PsA and healthy individuals.
Results: Across 44 immune cell populations, we observed significant immunophenotypic and immunometabolic changes in both diseases. B cell analysis revealed altered frequencies, different translational activity, and metabolic dependence in early developmental and antigen-experienced cell subsets. SCENITH profiling showed distinct metabolic signatures in CD4⁺ and CD8⁺ T cells, with more pronounced differences in naive and memory subsets. In fact, in SLE, T cells exhibited strong dependence on OXPHOS and limited sensitivity to glycolytic inhibition. Finally, PsA patients presented increased NKT-cell frequencies, indicating an involvement of lipid antigens.
Conclusion: Overall, these findings describe several immune and metabolic dysregulations in SLE and PsA patients, which could be used as potential biomarkers for disease progression and therapeutic intervention.
