A distinct population of Low-Density Granulocytes with unique features associated with subclinical vascular alterations in systemic lupus erythematosus

Background Low-density granulocytes (LDGs) play a key role in the pathogenesis of Systemic Lupus Erythematosus (SLE) and has been associated with vascular complications. Their heightened activation and NETosis may contribute to immune dysregulation and vascular inflammation. In this study, we analyzed a distinct myeloid subset excluded from standard LDG/monocyte gating due to high CD14 and CD15 co-expression. Methods Myeloid cell populations were quantified by flow cytometry in freshly isolated blood mononuclear cells (PBMC) from SLE patients (n=143), non-disease controls (n=42) and non-autoimmune atherosclerotic individuals (n=22). High-dimensional clustering and visualization of myeloid cells were performed using the FlowSOM algorithm. Circulating levels of cellular subsets were analyzed in relation to subclinical carotid arteriopathy determined by ultrasonography and/or previously documented clinical cardiovascular (CV)-disease. Results High-dimensional analysis identified a distinct CD14 + CD15 + CD16 + population in PBMC from patients and controls, separate from known LDG/monocytes. Phenotyping in 15 SLE patients characterized them as CD66b + CD15 + neutrophils displaying a CD14 + CD16 + HLADR + CD10 low profile, thus naming them APC-like neutrophils (nAPC-like). nAPC-like correlated with Th1 (ρ=0.230; p=0.006), Th17 (ρ=0.244; p=0.004) and Treg (ρ=-0.219; p=0.010) cells in SLE, as well as with SLEDAI and anti-dsDNA titers (all p