Background S100A11 (calgizzarin) is a member of the S100 protein family that participates in regulating number of biologic functions and is associated with oncogenesis and inflammation. Recent data suggest involvement of S100A11 in myocardial damage.
Objectives The aim of our study was to analyze the expression of S100A11 in patients with idiopathic inflammatory myopathies (IIMs) and its potential association with disease activity parameters and IIMs-related clinical features.
Methods immunohistochemistry in patients with polymyositis/dermatomyositis (PM/DM, n=5/6) and control individuals with myasthenia gravis (MG, n=5). S100A11 in plasma was measured by ELISA (Biovendor) in 112 patients with IIMs (PM, n=41; DM, n=41; and cancer associated myositis (CAM), n=30) and in 42 healthy controls (HC). Patients with PM/DM fulfilled Bohan and Peter diagnostic criteria and CAM was defined as cancer occurring within 3 years of the diagnosis of myositis. Clinical disease activity was assessed by myositis disease activity assessment (MYOACT), physician and patient's global activity using visual analogue scales (VAS), manual muscle testing (MMT) and health assessment questionnaire (HAQ). Muscle enzymes CK, LD, ALT, AST and CRP were measured by routine laboratory techniques. Autoantibodies were detected by immunoprecipitation.
Results S100A11 protein was up-regulated in the muscle from patients with IIMs compared to MG. In PM/DM patients, S100A11 was accumulated in the cytoplasm of regenerating and necrotizing muscle fibers and on the sarcolemma of most fibers. Only some mononuclear infiltrate cells showed S100A11 positivity. In patients with MG, S100A11 was detected on the sarcolemma only. Moreover, S100A11 was increased in plasma of patients with IIMs compared to HC (3.82 [1.47–72.9] vs. 2.84 [1.67–11.18] ng/ml; p=0.0076). When divided into groups, patients with DM and CAM showed significant elevation of plasma S100A11 compared to HC (4.10 [2.22–50.81] and 4.52 [1.53–9.11] vs. 2.84 [1.67–11.18] ng/ml; p=0.004 and p=0.02, respectively). Levels of S100A11 did not differ between PM and HC. In all patients, S100A11 correlated with LD (r=0.300, p=0.001), CK (r=0.217, p=0.025) and AST (r=0.343, p<0.001), with MYOACT (r=0.279, p=0.005) and with muscle, pulmonary and skin disease activity (r=0.199, p=0.040; r=0.224, p=0.025 and r=0.307, p=0.001). S100A11 levels were elevated in autoantibody-positive group compared to autoantibody-negative group of patients with IIMs (5.22 [1.45–69.29] vs 3.44 [1.58–12.12], p=0.010).
Conclusions S100A11 is up-regulated in the circulation of patients with IIMs and correlates with disease activity. Accumulation of S100A11 in the muscle of patients with myositis may indicate its potential role in the process of cell necrosis and fiber regeneration.
Acknowledgements Supported by grant 15–34065A of the Agency for Healthcare Research of the Czech Republic and MHCR 023728.
Disclosure of Interest None declared