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Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus

Tydén, Helena LU ; Lood, C. LU ; Gullstrand, B. LU ; Jönsen, A. LU ; Ivars, F. LU ; Leanderson, T. LU and Bengtsson, A. A. LU (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.

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author
organization
publishing date
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 Ltd
external identifiers
  • scopus:85007242847
  • wos:000392615400005
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
2018-04-08 04:52:46
@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},
  keyword      = {Anti-dsDNA antibodies,S100A12,S100A8/A9,SLE glomerulonephritis,systemic lupus erythematosus},
  language     = {eng},
  month        = {02},
  number       = {2},
  pages        = {139--149},
  publisher    = {SAGE Publications Ltd},
  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},
  volume       = {26},
  year         = {2017},
}