Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019
Abstract It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADA...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-37405-5 |
| _version_ | 1797789814863429632 |
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| author | Adrian A. N. Doevelaar Martin Bachmann Bodo Hölzer Felix S. Seibert Benjamin J. Rohn Panagiota Zgoura Oliver Witzke Ulf Dittmer Thorsten Brenner Krystallenia Paniskaki Serap Yilmaz Rita Dittmer Sonja Schneppenheim Jochen Wilhelm Ulrik Stervbo Nina Babel Ulrich Budde Timm H. Westhoff |
| author_facet | Adrian A. N. Doevelaar Martin Bachmann Bodo Hölzer Felix S. Seibert Benjamin J. Rohn Panagiota Zgoura Oliver Witzke Ulf Dittmer Thorsten Brenner Krystallenia Paniskaki Serap Yilmaz Rita Dittmer Sonja Schneppenheim Jochen Wilhelm Ulrik Stervbo Nina Babel Ulrich Budde Timm H. Westhoff |
| author_sort | Adrian A. N. Doevelaar |
| collection | DOAJ |
| description | Abstract It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding. In this observational prospective controlled multicenter study blood samples and clinical data of patients hospitalized for COVID-19 were collected from April to November 2020. The study included 156 individuals with 90 patients having confirmed COVID-19 of mild to critical severity. 30 healthy individuals and 36 critically ill ICU patients without COVID-19 served as controls. ADAMTS13 antibodies occurred in 31 (34.4%) COVID-19 patients. Antibodies occurred more often in critically ill COVID-19 patients (55.9%) than non-COVID-19 ICU patients and healthy controls (5.6% and 6.7%; p < 0.001), respectively. Generation of ADAMTS13 antibodies in COVID-19 was associated with lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p = 0.0041), increased disease severity (severe or critical in 90% vs. 62.3%, p = 0.019), and a trend to higher mortality (35.5% vs. 18.6%, p = 0.077). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen. Gel analysis of VWF multimers resembled the constellation in patients with TTP. The present study demonstrates for the first time, that generation of ADAMTS13 antibodies is frequent in COVID-19, associated with lower ADAMTS13 activity and increased risk of an adverse disease course. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections. |
| first_indexed | 2024-03-13T01:56:00Z |
| format | Article |
| id | doaj.art-fd43af590a5f4918ab69878c7b9e443f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T01:56:00Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-fd43af590a5f4918ab69878c7b9e443f2023-07-02T11:14:25ZengNature PortfolioScientific Reports2045-23222023-06-011311810.1038/s41598-023-37405-5Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019Adrian A. N. Doevelaar0Martin Bachmann1Bodo Hölzer2Felix S. Seibert3Benjamin J. Rohn4Panagiota Zgoura5Oliver Witzke6Ulf Dittmer7Thorsten Brenner8Krystallenia Paniskaki9Serap Yilmaz10Rita Dittmer11Sonja Schneppenheim12Jochen Wilhelm13Ulrik Stervbo14Nina Babel15Ulrich Budde16Timm H. Westhoff17Medical Department 1, University Hospital Marien Hospital Herne, Ruhr-University BochumDepartment of Intensive Care and Ventilatory Medicine, Asklepios Klinikum Hamburg HarburgMedical Department 1, University Hospital Marien Hospital Herne, Ruhr-University BochumMedical Department 1, University Hospital Marien Hospital Herne, Ruhr-University BochumMedical Department 1, University Hospital Marien Hospital Herne, Ruhr-University BochumMedical Department 1, University Hospital Marien Hospital Herne, Ruhr-University BochumDepartment of Infectiology, University Hospital Essen, University of Duisburg-EssenInstitute for Virology, University Hospital Essen, University of Duisburg-EssenDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University of Duisburg-EssenDepartment of Infectiology, University Hospital Essen, University of Duisburg-EssenDepartment of Intensive Care and Ventilatory Medicine, Asklepios Klinikum Hamburg HarburgDepartment of Hemostaseology, MEDILYS Laborgesellschaft mbHDepartment of Hemostaseology, MEDILYS Laborgesellschaft mbHDepartment of Hemostaseology, MEDILYS Laborgesellschaft mbHCenter for Translational Medicine, University Hospital Marien Hospital Herne, Ruhr-University BochumCenter for Translational Medicine, University Hospital Marien Hospital Herne, Ruhr-University BochumDepartment of Hemostaseology, MEDILYS Laborgesellschaft mbHMedical Department 1, University Hospital Marien Hospital Herne, Ruhr-University BochumAbstract It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding. In this observational prospective controlled multicenter study blood samples and clinical data of patients hospitalized for COVID-19 were collected from April to November 2020. The study included 156 individuals with 90 patients having confirmed COVID-19 of mild to critical severity. 30 healthy individuals and 36 critically ill ICU patients without COVID-19 served as controls. ADAMTS13 antibodies occurred in 31 (34.4%) COVID-19 patients. Antibodies occurred more often in critically ill COVID-19 patients (55.9%) than non-COVID-19 ICU patients and healthy controls (5.6% and 6.7%; p < 0.001), respectively. Generation of ADAMTS13 antibodies in COVID-19 was associated with lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p = 0.0041), increased disease severity (severe or critical in 90% vs. 62.3%, p = 0.019), and a trend to higher mortality (35.5% vs. 18.6%, p = 0.077). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen. Gel analysis of VWF multimers resembled the constellation in patients with TTP. The present study demonstrates for the first time, that generation of ADAMTS13 antibodies is frequent in COVID-19, associated with lower ADAMTS13 activity and increased risk of an adverse disease course. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections.https://doi.org/10.1038/s41598-023-37405-5 |
| spellingShingle | Adrian A. N. Doevelaar Martin Bachmann Bodo Hölzer Felix S. Seibert Benjamin J. Rohn Panagiota Zgoura Oliver Witzke Ulf Dittmer Thorsten Brenner Krystallenia Paniskaki Serap Yilmaz Rita Dittmer Sonja Schneppenheim Jochen Wilhelm Ulrik Stervbo Nina Babel Ulrich Budde Timm H. Westhoff Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019 Scientific Reports |
| title | Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019 |
| title_full | Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019 |
| title_fullStr | Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019 |
| title_full_unstemmed | Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019 |
| title_short | Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019 |
| title_sort | generation of potentially inhibitory autoantibodies to adamts13 in coronavirus disease 2019 |
| url | https://doi.org/10.1038/s41598-023-37405-5 |
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