Neutrophil Heterogeneity Identifies an Association of LAMP1 With Proliferative Lupus Nephritis
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) with limited biomarkers for early detection. While neutrophils contribute to SLE pathogenesis, their phenotypic heterogeneity in disease remains poorly characterized. Here, we used mass cytometry to profile blood neutrophils from patients with biopsy-confirmed proliferative LN and healthy controls. We identified a distinct population of activated neutrophils, marked by surface expression of lysosomal-associated membrane protein 1 (LAMP1/CD107a), that was virtually absent in healthy individuals. We demonstrate that LAMP1 resides intracellularly in resting neutrophils and translocates to the cell surface upon activation. Transcriptomic analysis revealed no difference in LAMP1 mRNA expression between patients with SLE and controls, confirming that surface LAMP1 reflects neutrophil activation rather than increased transcription. Soluble LAMP1 was significantly elevated in serum from patients with SLE compared with controls, with the highest levels in proliferative LN. In a large cohort of 225 patients with LN, urinary LAMP1 correlated with glomerular filtration rate, proteinuria, and histological activity indices. Together, our findings reveal LAMP1 as a marker of neutrophil activation in SLE and identify serum and urinary LAMP1 as potential noninvasive biomarkers for proliferative LN.
Authors
- Panagiotis Garantziotis
- James A. Lederer (ORCID: https://orcid.org/0000-0002-6445-252X)
- Andrea Fava (ORCID: https://orcid.org/0000-0001-6738-4836)
- Ricardo Grieshaber‐Bouyer (ORCID: https://orcid.org/0000-0002-2873-5135)
- Frank Y. Huang (ORCID: https://orcid.org/0000-0002-2163-9300)
- Georg Andreas Schett (ORCID: https://orcid.org/0000-0001-8740-9615)
- Lennard Ostendorf (ORCID: https://orcid.org/0000-0003-3553-6406)
- Deepak A. Rao (ORCID: https://orcid.org/0000-0001-9672-7746)
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Heidelberg University (DE)
- Johns Hopkins Medicine (US)
- University Hospital Heidelberg (DE)
- Leibniz Association (DE)
- Humboldt-Universität zu Berlin (DE)
- Universitätsklinikum Erlangen (DE)
- German Rheumatism Research Centre (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- European Journal of Immunology
- Published
- 2025-08-01
- DOI
- https://doi.org/10.1002/eji.70022
- Primary Topic
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bristol-Myers Squibb
- Pfizer
- GlaxoSmithKline
- Sanofi
- Rheumatology Research Foundation
- Lupus Research Alliance
- European Commission
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Else Kröner-Fresenius-Stiftung
- Boehringer Ingelheim Stiftung
- Berlin Institute of Health
- National Institutes of Health
- Takeda Pharmaceuticals International
- Leibniz-Gemeinschaft
- National Institute of Allergy and Infectious Diseases
- National Institute of Arthritis and Musculoskeletal and Skin Diseases