PO:01:005 Phenotypic, functional and metabolic assessment of myeloid derived supressor cells in systemic lupus erythematosus

Objectives Data regaring the involvement of myeloid-derived suppressor cells (MDSC) in systemic lupus erythematosus (SLE) remain limited and conflicting. We hypothesized that SLE MDSC are dysfunctional—losing suppressive capacity or becoming pro-inflammatory—driven by distinct immunometabolic programs. We aimed to quantify circulating MDSC and subsets, relate them to disease activity, test their impact on T-cell proliferation, assess their metabolic profle, and compare single-cell transcriptomes with healthy donors.Methods We conducted a prospective single-center study of adults meeting ACR/EULAR 2019 and/or SLICC criteria (SLEDAI-2K > 1) at baseline (M0), 3 months (M3), and 6 months (M6). PBMC were analyzed by 27-parameter flow cytometry. MDSC were gated as CD19–CD3–HLA-DR–CD11bhiCD33+ and assigned to monocytic (M-), granulocytic (G-), or early (E-) subsets according to the expression of CD14 and CD15. MDSC were purified by magnetic sorting (HLA-DR and lineage depletion, CD11b selection) and co-cultured with anti-CD3/CD28-activated T cells. An intracellular panel quantified metabolic proteins (HK1, GLUT1, CPT1A, PRDX2, ASS1, ACAC, ATP5A). A public single-cell RNA-seq database (162 SLE/99 healthy donors) was re-analyzed focusing on myeloid HLA-DR low cells. This study was approved by local ethics committee, and registered on ClinicalTrials.com ( NCT05424627).Results We enrolled 21 SLE patients (19 women; median age 39) and 8 controls. Total MDSC were increased in SLE (median 0.87% vs 0.27% of viable PBMC; p=0.005), mainly due to M-MDSC (0.08% vs 0.02%; p=0.03). Longitudinally, MDSC rose at M3 and M6, largely driven by G-MDSC expansion. After Benjamini–Hochberg correction, CD38 intensity on G-MDSC correlated with articular involvement and inflammatory arthralgia ( rho =0.79; q