{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:53:49Z","timestamp":1789736029422,"version":"4.0.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":2031,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T00:00:00Z","timestamp":1590624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Berlin-Brandenburg Center for Regenerative Therapies - BCRT","award":["0313911"],"award-info":[{"award-number":["0313911"]}]},{"DOI":"10.13039\/100008792","name":"Novartis Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Berlin-Brandenburg Center for Regenerative Therapies \u2013 BCRT","award":["0313911"],"award-info":[{"award-number":["0313911"]}]},{"DOI":"10.13039\/100008792","name":"Novartis Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>Serum S100A8\/A9 levels were analysed in patients with a recent onset of MC [\u2264 30 days, n = 32; ejection fraction (EF): 45.4 \u00b1 12.9%], dilated cardiomyopathy patients with inflammation (n = 112; EF: 29.0 \u00b1 11.4%), or without inflammation (n = 58; EF: 26.6 \u00b1 9.3%), and controls (n = 25; EF: 68.5 \u00b1 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 \u00b1 1670 ng\/mL vs. controls: 426 \u00b1 307 ng\/mL; P &amp;lt; 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\u20131]). 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 \u00b1 1843 ng\/mL vs. T2: 888.8 \u00b1 513.7 ng\/mL; P = 0.00052) was associated with a reduced cardiac inflammation (CD3 T1: 70.02 \u00b1 107.4 cells per square millimetre vs. T2: 59.18 \u00b1 182.5 cells per square millimetre; P = 0.0342, lymphocyte function-associated antigen-1 T1: 133.5 \u00b1 187.1 cells per square millimetre vs. T2: 74.12 \u00b1 190.5 cells per square millimetre; P = 0.0186, and macrophage-1 antigen T1: 132.6 \u00b1 129.5 cells per square millimetre vs. T2: 54.41 \u00b1 65.16 cells per square millimetre; P = 0.0015). Serum S100A8\/A9 levels were only slightly increased in patients within the chronic phase of MC and in heart failure patients without inflammation vs. controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Serum S100A8\/A9 might serve as an additional tool in the diagnostic workup of suspected acute MC patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12760","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T04:50:05Z","timestamp":1590641405000},"page":"1442-1451","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Serum Alarmin S100A8\/S100A9 Levels and Its Potential Role as Biomarker in Myocarditis"],"prefix":"10.1093","volume":"7","author":[{"given":"Irene","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Berlin Institute of Health (BIH) & Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum , Berlin ,","place":["Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), partner site Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vogl","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of M\u00fcnster , M\u00fcnster ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"K\u00fchl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Krannich","sequence":"additional","affiliation":[{"name":"Institute of Medical Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aron","family":"Banks","sequence":"additional","affiliation":[{"name":"Cardiotropic Lab , Miami, FL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Trippel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Noutsias","sequence":"additional","affiliation":[{"name":"Mid-German Heart Center, Division of Cardiology, Angiology and Intensive Medical Care, Martin-Luther-University Halle-Wittenberg , Halle (Saale) ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Maisel","sequence":"additional","affiliation":[{"name":"FACC, University of California San Diego , San Diego, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"van Linthout","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health (BIH) & Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum , Berlin ,","place":["Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), partner site Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Tsch\u00f6pe*","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health (BIH) & Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum , Berlin ,","place":["Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), partner site Berlin , Berlin ,","place":["Germany"]},{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,28]]},"reference":[{"key":"2026012115032824500_ehf212760-bib-0001","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/eurheartj\/eht210","article-title":"European Society of Cardiology Working Group on M and Pericardial D. 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