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2017 ; 19
(1
): 79
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Calgizzarin (S100A11): a novel inflammatory mediator associated with disease
activity of rheumatoid arthritis
#MMPMID28446208
Andrés Cerezo L
; ?umová B
; Prajzlerová K
; Veigl D
; Damgaard D
; Nielsen CH
; Pavelka K
; Vencovský J
; ?enolt L
Arthritis Res Ther
2017[Apr]; 19
(1
): 79
PMID28446208
show ga
BACKGROUND: Calgizzarin (S100A11) is a member of the S100 protein family that
acts in different tumors by regulating a number of biologic functions. Recent
data suggest its association with low-grade inflammation in osteoarthritis (OA).
The aim of our study is to compare S100A11 expression in the synovial tissues,
synovial fluid and serum of patients with rheumatoid arthritis (RA) and
osteoarthritis (OA) and to characterize the potential association between S100A11
and disease activity. METHODS: S100A11 protein expression was detected in
synovial tissue from patients with RA (n?=?6) and patients with OA (n?=?6) by
immunohistochemistry and immunofluorescence. Serum and synovial fluid S100A11
levels were measured by ELISA in patients with RA (n?=?40) and patients with OA
(n?=?34). Disease activity scores in 28 joints based on C-reactive protein
(DAS28-CRP) were used to assess disease activity. Cytokine content in peripheral
blood mononuclear cells (PBMCs), synovial fibroblasts (SFs) and synovial fluid
was analysed by ELISA, western blotting or cytometric bead array. RESULTS:
S100A11 expression was significantly up-regulated in the synovial lining and
sublining layers (p?0.01) and vessels (p?0.05) of patients with RA compared
to patients with OA, and was associated with fibroblasts and T cells. S100A11 was
significantly increased in synovial fluid (p?0.0001) but not in serum
(p?=?0.158) from patients with RA compared to patients with OA when adjusted for
age and sex. Synovial fluid S100A11 correlated with DAS28 (r?=?0.350, p?=?0.027),
serum CRP (r?=?0.463, p?=?0.003), synovial fluid leukocyte count (r?=?0.677,
p?0.001), anti-cyclic citrullinated peptide antibodies (anti-CCP) (r?=?0.424,
p?=?0.006) and IL-6 (r?=?0.578, p?=?0.002) and IL-8 (r?=?0.740, p?0.001) in
synovial fluid from patients with RA. PBMCs and SFs isolated from patients with
RA synthesized and spontaneously secreted higher levels of S100A11 in comparison
with PBMCs and SFs from patients with OA (p?=?0.011 and 0.03, respectively).
S100A11 stimulated the production of the pro-inflammatory cytokine IL-6 by PBMCs
(p?0.05) and SFs (p?0.01). CONCLUSIONS: Our data provide the first evidence
of S100A11 up-regulation and its association with inflammation and disease
activity in patients with RA.