{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:24:40Z","timestamp":1792448680418,"version":"4.5.0"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n High-dimensional analysis identified a distinct CD14\n +<\/jats:sup>\n CD15\n +<\/jats:sup>\n CD16\n +<\/jats:sup>\n population in PBMC from patients and controls, separate from known LDG\/monocytes. Phenotyping in 15 SLE patients characterized them as CD66b\n +<\/jats:sup>\n CD15\n +<\/jats:sup>\n neutrophils displaying a CD14\n +<\/jats:sup>\n CD16\n +<\/jats:sup>\n HLADR\n +<\/jats:sup>\n CD10\n low<\/jats:sup>\n profile, thus naming them APC-like neutrophils (nAPC-like). nAPC-like correlated with Th1 (\u03c1=0.230; p=0.006), Th17 (\u03c1=0.244; p=0.004) and Treg (\u03c1=-0.219; p=0.010) cells in SLE, as well as with SLEDAI and anti-dsDNA titers (all p&lt;0.001). Moreover, nAPC-like were increased in patients and controls with traditional CV-risk factors or clinical\/subclinical CV-disease. A minor CD16\n dim_<\/jats:sup>\n nAPC-like subset (CD10\n neg<\/jats:sup>\n CD66b\n high<\/jats:sup>\n CD15\n low<\/jats:sup>\n ), suggestive of an immature status, was expanded in SLE and correlated with serum IL-6 and BLyS (p&lt;0.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1794775","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:44:29Z","timestamp":1779342269000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["A distinct population of Low-Density Granulocytes with unique features associated with subclinical vascular alterations in systemic lupus erythematosus"],"prefix":"10.3389","volume":"17","author":[{"given":"Ux\u00eda","family":"Tob\u00edo-Parada","sequence":"first","affiliation":[{"name":"Group of Basic and Translational Research in Inflammatory Diseases. Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo","place":["Oviedo, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Rodr\u00edguez-Carrio","sequence":"additional","affiliation":[{"name":"Group of Basic and Translational Research in Inflammatory Diseases. Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo","place":["Oviedo, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleida","family":"Mart\u00ednez-Zapico","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Central de Asturias","place":["Oviedo, Spain"]},{"name":"Department of Neurology, Hospital Universitario Central de Asturias","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel I.","family":"P\u00e9rez-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","place":["Oviedo, Spain"]},{"name":"Department of Neurology, Hospital Universitario Central de Asturias","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Su\u00e1rez-D\u00edaz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","place":["Oviedo, Spain"]},{"name":"Department of Internal Medicine, Hospital Universitario Central de Asturias","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Group of Basic and Translational Research in Inflammatory Diseases. Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo","place":["Oviedo, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Group of Basic and Translational Research in Inflammatory Diseases. Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo","place":["Oviedo, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1093\/rheumatology\/keaa225","article-title":"Low-density granulocytes and monocytes as biomarkers of cardiovascular risk in systemic lupus erythematosus","volume":"59","author":"L\u00f3pez","year":"2020","journal-title":"Rheumatol (Oxford)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"13230","DOI":"10.1038\/s41598-019-49429-x","article-title":"A subset of low density granulocytes is associated with vascular calcification in chronic kidney disease patients","volume":"9","author":"Rodr\u00edguez-Carrio","year":"2019","journal-title":"Sci Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/art.43019","article-title":"Exploring the role of neutrophil extracellular traps in systemic lupus erythematosus: a clinical case study and comprehensive review","volume":"77","author":"Kaplan","year":"2025","journal-title":"Arthritis Rheumatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1002\/art.1780400928","article-title":"Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus","volume":"40","author":"Hochberg","year":"1997","journal-title":"Arthritis Rheum"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1159\/000081812","article-title":"Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). 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