Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditis
Abstract 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 seru...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-08-01
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| Series: | ESC Heart Failure |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ehf2.12760 |
| _version_ | 1828967683195928576 |
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| author | Irene Müller Thomas Vogl Uwe Kühl Alexander Krannich Aron Banks Tobias Trippel Michel Noutsias Alan S. Maisel Sophie vanLinthout Carsten Tschöpe |
| author_facet | Irene Müller Thomas Vogl Uwe Kühl Alexander Krannich Aron Banks Tobias Trippel Michel Noutsias Alan S. Maisel Sophie vanLinthout Carsten Tschöpe |
| author_sort | Irene Müller |
| collection | DOAJ |
| description | Abstract 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 onset 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 Blood samples were collected at Time Point 1 (T1), where also endomyocardial biopsies (EMBs) were withdrawn.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: 888.8 ± 513.7 ng/mL; P = 0.00052) was associated with a reduced cardiac inflammation (CD3 T1: 70.02 ± 107.4 cells per square millimetre vs. T2: 59.18 ± 182.5 cells per square millimetre; P = 0.0342, lymphocyte function‐associated antigen‐1 T1: 133.5 ± 187.1 cells per square millimetre vs. T2: 74.12 ± 190.5 cells per square millimetre; P = 0.0186, and macrophage‐1 antigen T1: 132.6 ± 129.5 cells per square millimetre vs. T2: 54.41 ± 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. Conclusions Serum S100A8/A9 might serve as an additional tool in the diagnostic workup of suspected acute MC patients. |
| first_indexed | 2024-12-14T11:56:50Z |
| format | Article |
| id | doaj.art-ede98efa1d364ea89de38dd1f70a858a |
| institution | Directory Open Access Journal |
| issn | 2055-5822 |
| language | English |
| last_indexed | 2024-12-14T11:56:50Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj.art-ede98efa1d364ea89de38dd1f70a858a2022-12-21T23:02:06ZengWileyESC Heart Failure2055-58222020-08-01741442145110.1002/ehf2.12760Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditisIrene Müller0Thomas Vogl1Uwe Kühl2Alexander Krannich3Aron Banks4Tobias Trippel5Michel Noutsias6Alan S. Maisel7Sophie vanLinthout8Carsten Tschöpe9Berlin Institute of Health (BIH) & Berlin‐Brandenburg Center for Regenerative Therapies (BCRT) Charité – Universitätsmedizin Berlin, Campus Virchow Klinikum Berlin GermanyDepartment of Immunology University of Münster Münster GermanyDepartment of Internal Medicine and Cardiology Charité – Universitätsmedizin Berlin, Campus Virchow Klinikum Berlin GermanyInstitute of Medical Immunology Charité – Universitätsmedizin Berlin Berlin GermanyCardiotropic Lab Miami FL USADepartment of Internal Medicine and Cardiology Charité – Universitätsmedizin Berlin, Campus Virchow Klinikum Berlin GermanyMid‐German Heart Center, Division of Cardiology, Angiology and Intensive Medical Care Martin‐Luther‐University Halle‐Wittenberg Halle (Saale) GermanyFACC University of California San Diego San Diego CA USABerlin Institute of Health (BIH) & Berlin‐Brandenburg Center for Regenerative Therapies (BCRT) Charité – Universitätsmedizin Berlin, Campus Virchow Klinikum Berlin GermanyBerlin Institute of Health (BIH) & Berlin‐Brandenburg Center for Regenerative Therapies (BCRT) Charité – Universitätsmedizin Berlin, Campus Virchow Klinikum Berlin GermanyAbstract 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 onset 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: 888.8 ± 513.7 ng/mL; P = 0.00052) was associated with a reduced cardiac inflammation (CD3 T1: 70.02 ± 107.4 cells per square millimetre vs. T2: 59.18 ± 182.5 cells per square millimetre; P = 0.0342, lymphocyte function‐associated antigen‐1 T1: 133.5 ± 187.1 cells per square millimetre vs. T2: 74.12 ± 190.5 cells per square millimetre; P = 0.0186, and macrophage‐1 antigen T1: 132.6 ± 129.5 cells per square millimetre vs. T2: 54.41 ± 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. Conclusions Serum S100A8/A9 might serve as an additional tool in the diagnostic workup of suspected acute MC patients.https://doi.org/10.1002/ehf2.12760S100A8/S100A9MyocarditisEndomyocardial biopsy |
| spellingShingle | Irene Müller Thomas Vogl Uwe Kühl Alexander Krannich Aron Banks Tobias Trippel Michel Noutsias Alan S. Maisel Sophie vanLinthout Carsten Tschöpe Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditis ESC Heart Failure S100A8/S100A9 Myocarditis Endomyocardial biopsy |
| title | Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditis |
| title_full | Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditis |
| title_fullStr | Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditis |
| title_full_unstemmed | Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditis |
| title_short | Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditis |
| title_sort | serum alarmin s100a8 s100a9 levels and its potential role as biomarker in myocarditis |
| topic | S100A8/S100A9 Myocarditis Endomyocardial biopsy |
| url | https://doi.org/10.1002/ehf2.12760 |
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