Abstract
IntroductionThe aim was to evaluate S100A4 protein as a biomarker of disease activity and potential cancer development in patients with myositis.MethodsSerum levels of S100A4 were determined in 43 dermatomyositis (DM), 39 polymyositis (PM) and 22 cancer associated myositis (CAM) patients as well as in 77 healthy controls. The associations between S100A4 levels, inflammation, disease activity, muscle strength and cancer development were evaluated.ResultsAll myositis patients had significantly higher serum levels of S100A4 protein compared to healthy controls (median (IQR): 31.5 (17.4 to 59.5) versus 23.8 (14.5 to 33.7) ng/ml, P <0.05). In patients with PM, serum levels of S100A4 protein were significantly higher than in healthy controls (41.6 (24.2 to 123.1) versus 23.8 (14.5 to 33.7) ng/ml; P <0.001) as well as in patients with DM (26.7 (11.3 to 47.5) ng/ml; P <0.05). The levels of S100A4 were comparable between myositis with and without cancer. In all myositis patients, serum S100A4 levels correlated with MYOsitis disease ACTivity assessment (MYOACT) score (r = 0.34; P = 0.001), constitutional (r = 0.30; P = 0.003), pulmonary (r = 0.43; P = 0.0001) and extramuscular disease activity (r = 0.36; P = 0.0001), as well as with creatine phosphokinase (r = 0.27; P = 0.015) and lactate dehydrogenase (r = 0.37; P = 0.002) or c-reactive protein (CRP) levels (r = 0.24; P = 0.038). Multiple regression analysis showed significant association between S100A4 serum levels and extramuscular disease activity (β = 0.552; P = 0.002) in PM patients and with MYOACT (β = 0.557; P = 0.003) and CRP levels (β = 0.391; P = 0.029) in DM patients.ConclusionsCirculating levels of S100A4 are elevated in patients with myositis and associate with several disease activity parameters, particularly with extramuscular components. No relation between S100A4 levels and presence of cancer associated myositis was found.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0468-2) contains supplementary material, which is available to authorized users.
Highlights
The aim was to evaluate S100A4 protein as a biomarker of disease activity and potential cancer development in patients with myositis
In this study we demonstrated 1) no relationship between S100A4 and cancer-associated myositis; 2) increased S100A4 serum levels in myositis patients; 3) a relationship between S100A4 and some myositis-specific and myositisassociated autoantibodies; and 4) association between S100A4 levels and several features of myositis disease activity, with extramuscular symptoms
Given the association of myositis, and dermatomyositis in particular, with increased risk of cancer development [6,7], it may be surprising that we have not observed higher serum levels of S100A4 in patients with cancerassociated myositis and that S100A4 levels were even lower in those with anti-TIF1 autoantibodies, a biomarker that identifies a large proportion of myositis patients with concomitant cancer [30]
Summary
The aim was to evaluate S100A4 protein as a biomarker of disease activity and potential cancer development in patients with myositis. Idiopathic inflammatory myopathy is a heterogeneous group of chronic muscle disorders with main subtypes including polymyositis (PM), dermatomyositis (DM), inclusion body myositis and necrotizing myopathy [1]. We and others have recently demonstrated increased expression of S100A4 at local sites of inflammation in several chronic inflammatory and autoimmune diseases [17,18,19,20,21], including muscle tissue from patients with idiopathic inflammatory myopathies [22]. We have previously found increased circulating levels of S100A4 in patients with rheumatoid arthritis (RA) in comparison with control individuals and demonstrated a positive correlation between S100A4 and disease activity in RA [23]
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