Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus
(2017) In Lupus 26(2). p.139-149- 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... (More)
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.
(Less)
- author
- Tydén, Helena LU ; Lood, C. LU ; Gullstrand, B. LU ; Jönsen, A. LU ; Ivars, F. LU ; Leanderson, T. LU and Bengtsson, A. A. LU
- organization
- publishing date
- 2017-02-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Anti-dsDNA antibodies, S100A12, S100A8/A9, SLE glomerulonephritis, systemic lupus erythematosus
- in
- Lupus
- volume
- 26
- issue
- 2
- pages
- 11 pages
- publisher
- SAGE Publications
- external identifiers
-
- pmid:27407135
- wos:000392615400005
- scopus:85007242847
- ISSN
- 0961-2033
- DOI
- 10.1177/0961203316655208
- language
- English
- LU publication?
- yes
- id
- 94f540f9-0540-4b46-858d-20abc4b7f1e1
- date added to LUP
- 2017-01-13 13:03:39
- date last changed
- 2024-04-05 13:04:52
@article{94f540f9-0540-4b46-858d-20abc4b7f1e1,
abstract = {{<p>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.</p>}},
author = {{Tydén, Helena and Lood, C. and Gullstrand, B. and Jönsen, A. and Ivars, F. and Leanderson, T. and Bengtsson, A. A.}},
issn = {{0961-2033}},
keywords = {{Anti-dsDNA antibodies; S100A12; S100A8/A9; SLE glomerulonephritis; systemic lupus erythematosus}},
language = {{eng}},
month = {{02}},
number = {{2}},
pages = {{139--149}},
publisher = {{SAGE Publications}},
series = {{Lupus}},
title = {{Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus}},
url = {{http://dx.doi.org/10.1177/0961203316655208}},
doi = {{10.1177/0961203316655208}},
volume = {{26}},
year = {{2017}},
}