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 Conclusions: Our findings reveal a previously unrecognized LDG subset with neutrophil and APC-like features that may contribute to immune dysregulation and subclinical carotid arteriopathy in SLE and non-autoimmune individuals.