title: Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus.
abstract: Objectives Systemic lupus erythematosus (SLE) is associated with elevated levels of S100A8/A9, pro-inflammatory proteins mainly secreted by activated polymorphonuclear neutrophils (PMNs). The underlying mechanisms for increased S100A8/A9 levels and their relation to the clinical phenotype have not been carefully investigated. We assessed S100A8/A9 and S100A12 levels in SLE patient sera in relation to disease activity, clinical phenotype, presence of anti-dsDNA antibodies and ability to promote phagocytosis of necrotic cells (NCs) by PMNs. Methods Serum levels of S100A8/A9 and S100A12 were measured by ELISA in paired samples of 100 SLE patients at time points of higher and lower disease activity. Serum-mediated phagocytosis of NCs by PMNs was analysed by flow cytometry. Clinical data were recorded at time points of blood sampling. Results Serum levels of S100A8/A9 and S100A12 were increased in SLE patients with high disease activity compared to paired samples at low disease activity ( p = 0.01 and p = 0.008, respectively). Elevated levels of S100A8/A9 were particularly seen in patients with anti-dsDNA antibodies ( p = 0.01) and glomerulonephritis before treatment ( p = 0.02). Immunosuppressive therapy was associated with a reduction of S100A8/A9 serum levels ( p = 0.002). The ability of serum to support phagocytosis of NCs by PMNs was related to increased S100A8/A9 levels ( p = 0.01). Conclusions Elevated serum levels of S100A8/A9 may be used to monitor disease activity and response to treatment in SLE patients, especially in patients with glomerulonephritis. S100A12 may be a marker of disease activity in SLE. Increased S100A8/A9 levels may reflect immune-pathological processes involving phagocytosis of immune complexes by PMNs.
authors.affiliation: 1 Department of Clinical Sciences, Division of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Tydén
authors.affiliation: 1 Department of Clinical Sciences, Division of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Lood
authors.affiliation: 1 Department of Clinical Sciences, Division of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Gullstrand
authors.affiliation: 1 Department of Clinical Sciences, Division of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Jönsen
authors.affiliation: 2 Department of Experimental Medical Science, Immunology Group, Lund University, Lund, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Ivars
authors.affiliation: 2 Department of Experimental Medical Science, Immunology Group, Lund University, Lund, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Leanderson
authors.affiliation: 1 Department of Clinical Sciences, Division of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: A A
authors.initials: AA
authors.lastname: Bengtsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D040501:Calgranulin A / Q000097:blood; D040502:Calgranulin B / Q000097:blood; D004247:DNA / Q000276:immunology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D008181:Lupus Nephritis / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D009418:S100 Proteins / Q000097:blood*; D000067616:S100A12 Protein / Q000097:blood; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D004247:DNA
keywords: Anti-dsDNA antibodies; S100A12; S100A8/A9; SLE glomerulonephritis; systemic lupus erythematosus