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Metastasin S100A4 is increased in proportion to radiographic damage in patients with RA.

Erlandsson, Malin C; Forslind, Kristina LU ; Andersson, Sofia E M; Lund, Annelie and Bokarewa, Maria I (2012) In Rheumatology (Oxford, England) 51(5). p.932-940
Abstract
Objective. To assess the potential of metastasin S100A4 as a biological marker in patients with RA.Methods. A total of 87 unselected patients with established RA (disease duration 2-44 years) and treated with MTX and infliximab at a single rheumatology centre were included in a cross-sectional study. Radiographs of hands and feet were taken prior to infliximab treatment and at inclusion (time interval 48 ± 27 months) and scored for the radiographic damage. S100A4 levels were analysed in relation to radiographic damage, clinical disease activity (DAS-28), inflammation (IL-6, CRP, ESR), bone and cartilage markers [MMP-3, COMP, C-telopeptide of type I collagen (CTX-I)] and proto-oncogenes [survivin, insulin-like growth factor 1 (IGF-1), Flt3... (More)
Objective. To assess the potential of metastasin S100A4 as a biological marker in patients with RA.Methods. A total of 87 unselected patients with established RA (disease duration 2-44 years) and treated with MTX and infliximab at a single rheumatology centre were included in a cross-sectional study. Radiographs of hands and feet were taken prior to infliximab treatment and at inclusion (time interval 48 ± 27 months) and scored for the radiographic damage. S100A4 levels were analysed in relation to radiographic damage, clinical disease activity (DAS-28), inflammation (IL-6, CRP, ESR), bone and cartilage markers [MMP-3, COMP, C-telopeptide of type I collagen (CTX-I)] and proto-oncogenes [survivin, insulin-like growth factor 1 (IGF-1), Flt3 ligand].Results. High levels of S100A4 were associated with severe radiographic damage (OR = 3.40, P = 0.025), non-response to infliximab (OR = 4.63, P = 0.003), presence of antibodies to infliximab (OR = 6.24, P = 0.003) and high levels of Flt3 ligand (OR = 2.73, P = 0.04). Regression analysis showed that high S100A4 was predictive for radiographic progression during infliximab treatment [positive predictive value (PPV) 0.68, P = 0.05]. Low levels of S100A4 were associated with response to infliximab (OR = 2.67, P = 0.049), clinical remission (OR = 4.01, P = 0.0047) and negative RF (OR = 9.22, P = 0.0047). S100A4 correlated with survivin (r = 0.71, P > 0.0001).Conclusion. S100A4 levels are increased in proportion to radiographic damage and its further progression in RA patients. High S100A4 levels were associated with a poor clinical response to infliximab and high rate of anti-infliximab antibodies. The finding of a correlation between S100A4 and survivin and Flt3 ligand suggests that these proteins may represent a new cluster of biomarkers predicting radiographic progression and poor treatment response in RA patients. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Rheumatology (Oxford, England)
volume
51
issue
5
pages
932 - 940
publisher
Oxford University Press
external identifiers
  • WOS:000303159800026
  • PMID:22258387
  • Scopus:84860255148
ISSN
1462-0332
DOI
10.1093/rheumatology/ker362
language
English
LU publication?
yes
id
7838f250-54d9-4bc6-ba24-909154acbd68 (old id 2336195)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22258387?dopt=Abstract
date added to LUP
2012-02-01 22:18:45
date last changed
2016-10-13 15:12:30
@misc{7838f250-54d9-4bc6-ba24-909154acbd68,
  abstract     = {Objective. To assess the potential of metastasin S100A4 as a biological marker in patients with RA.Methods. A total of 87 unselected patients with established RA (disease duration 2-44 years) and treated with MTX and infliximab at a single rheumatology centre were included in a cross-sectional study. Radiographs of hands and feet were taken prior to infliximab treatment and at inclusion (time interval 48 ± 27 months) and scored for the radiographic damage. S100A4 levels were analysed in relation to radiographic damage, clinical disease activity (DAS-28), inflammation (IL-6, CRP, ESR), bone and cartilage markers [MMP-3, COMP, C-telopeptide of type I collagen (CTX-I)] and proto-oncogenes [survivin, insulin-like growth factor 1 (IGF-1), Flt3 ligand].Results. High levels of S100A4 were associated with severe radiographic damage (OR = 3.40, P = 0.025), non-response to infliximab (OR = 4.63, P = 0.003), presence of antibodies to infliximab (OR = 6.24, P = 0.003) and high levels of Flt3 ligand (OR = 2.73, P = 0.04). Regression analysis showed that high S100A4 was predictive for radiographic progression during infliximab treatment [positive predictive value (PPV) 0.68, P = 0.05]. Low levels of S100A4 were associated with response to infliximab (OR = 2.67, P = 0.049), clinical remission (OR = 4.01, P = 0.0047) and negative RF (OR = 9.22, P = 0.0047). S100A4 correlated with survivin (r = 0.71, P > 0.0001).Conclusion. S100A4 levels are increased in proportion to radiographic damage and its further progression in RA patients. High S100A4 levels were associated with a poor clinical response to infliximab and high rate of anti-infliximab antibodies. The finding of a correlation between S100A4 and survivin and Flt3 ligand suggests that these proteins may represent a new cluster of biomarkers predicting radiographic progression and poor treatment response in RA patients.},
  author       = {Erlandsson, Malin C and Forslind, Kristina and Andersson, Sofia E M and Lund, Annelie and Bokarewa, Maria I},
  issn         = {1462-0332},
  language     = {eng},
  number       = {5},
  pages        = {932--940},
  publisher    = {ARRAY(0xad27db0)},
  series       = {Rheumatology (Oxford, England)},
  title        = {Metastasin S100A4 is increased in proportion to radiographic damage in patients with RA.},
  url          = {http://dx.doi.org/10.1093/rheumatology/ker362},
  volume       = {51},
  year         = {2012},
}