Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditis

Irene Müller, Thomas Vogl, Uwe Kühl, Alexander Krannich, Aron Banks, Tobias Trippel, Michel Noutsias, Alan S. Maisel, Sophie Van Linthout, Carsten Tschöpe, Universitätsbibliothek Der FU Berlin
Aims: The alarmin S100A8/S100A9 (S100A8/A9) is released by activated monocytes/macrophages and neutrophils in the setting lymphocytic myocarditis (MC). We recently demonstrated its therapeutic potential in experimental acute MC. Now, we investigated the diagnostic relevance of S100A8/A9 serum levels in patients with suspected acute and chronic MC and in patients with heart failure without cardiac inflammation. Methods and Results: Serum S100A8/A9 levels were analysed in patients with a recent
more » ... set of MC [≤ 30 days, n = 32; ejection fraction (EF): 45.4 ± 12.9%], dilated cardiomyopathy patients with inflammation (n = 112; EF: 29.0 ± 11.4%), or without inflammation (n = 58; EF: 26.6 ± 9.3%), and controls (n = 25; EF: 68.5 ± 4.6%), by using specific ELISAs. Blood samples were collected at Time Point 1 (T1), where also endomyocardial biopsies (EMBs) were withdrawn. Patients with a recent onset of MC showed a 4.6-fold increase in serum S100A8/A9 levels vs. controls (MC: 1948 ± 1670 ng/mL vs. controls: 426 ± 307 ng/mL; P < 0.0001). Serum S100A8/A9 correlated with the disease activity, represented by EMB-derived counts of inflammatory cells (CD3: r = 0.486, P = 0.0047, lymphocyte function-associated antigen-1: r = 0.558, P = 0.0009, macrophage-1 antigen: r = 0.434, P = 0.013), the EMB mRNA levels of S100A8, S100A9 (r = 0.541, P = 0.002), and left ventricular ejection fraction (LVEF: r = 0.498, P = 0.0043). EMB immunofluorescence co-stainings display macrophages/monocytes and neutrophils as the main source of S100A8 and S100A9 in recent onset MC. The diagnostic value of serum alarmin levels (cut-off 583 ng/mL) was characterized by a specificity of 92%, a sensitivity of 90.6%, positive predictive value of 93.5%, negative predictive value of 88.5%, and an accuracy of 0.949 (95% confidence interval [0.89-1]). In a subgroup of MC patients, S100A8/A9 serum levels and EMBs at T1 (n = 12) and a follow-up visit (T2, n = 12, mean follow-up 8.5 months) were available. A fall of serum S100A8/A9 (T1: 2208 ± 1843 ng/mL vs. T2: 888 [...]
doi:10.17169/refubium-32321 fatcat:n3ro7gp4fbdqbmrlwzajuozhje