Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms
Abstract Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) mol...
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Nature Portfolio
2025-01-01
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| Series: | npj Systems Biology and Applications |
| Online Access: | https://doi.org/10.1038/s41540-025-00488-z |
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| author | Dennyson Leandro M. Fonseca Maj Jäpel Michael Adu Gyamfi Igor Salerno Filgueiras Gabriela Crispim Baiochi Yuri Ostrinski Gilad Halpert Yael Bublil Lavi Elroy Vojdani Thayna Silva-Sousa Júlia Nakanishi Usuda Juan Carlo Santos e Silva Paula P. Freire Adriel Leal Nóbile Anny Silva Adri Pedro Marçal Barcelos Yohan Lucas Gonçalves Corrêa Fernando Yuri Nery do Vale Letícia Oliveira Lopes Solveig Lea Schmidt Xiaoqing Wang Carl Vahldieck Benedikt Fels Lena F. Schimke Gustavo Cabral-Miranda Mario Hiroyuki Hirata Taj Ali AKhan Yen-Rei A. Yu Rodrigo JS Dalmolin Howard Amital Aristo Vojdani Haroldo Dutra Dias Helder Nakaya Hans D. Ochs Jonathan I. Silverberg Jason Zimmerman Israel Zyskind Avi Z. Rosenberg Kai Schulze-Forster Harald Heidecke Rusan Catar Guido Moll Alexander Hackel Kristina Kusche-Vihrog Yehuda Shoenfeld Gabriela Riemekasten Reza Akbarzadeh Alexandre H. C. Marques Otavio Cabral-Marques |
| author_facet | Dennyson Leandro M. Fonseca Maj Jäpel Michael Adu Gyamfi Igor Salerno Filgueiras Gabriela Crispim Baiochi Yuri Ostrinski Gilad Halpert Yael Bublil Lavi Elroy Vojdani Thayna Silva-Sousa Júlia Nakanishi Usuda Juan Carlo Santos e Silva Paula P. Freire Adriel Leal Nóbile Anny Silva Adri Pedro Marçal Barcelos Yohan Lucas Gonçalves Corrêa Fernando Yuri Nery do Vale Letícia Oliveira Lopes Solveig Lea Schmidt Xiaoqing Wang Carl Vahldieck Benedikt Fels Lena F. Schimke Gustavo Cabral-Miranda Mario Hiroyuki Hirata Taj Ali AKhan Yen-Rei A. Yu Rodrigo JS Dalmolin Howard Amital Aristo Vojdani Haroldo Dutra Dias Helder Nakaya Hans D. Ochs Jonathan I. Silverberg Jason Zimmerman Israel Zyskind Avi Z. Rosenberg Kai Schulze-Forster Harald Heidecke Rusan Catar Guido Moll Alexander Hackel Kristina Kusche-Vihrog Yehuda Shoenfeld Gabriela Riemekasten Reza Akbarzadeh Alexandre H. C. Marques Otavio Cabral-Marques |
| author_sort | Dennyson Leandro M. Fonseca |
| collection | DOAJ |
| description | Abstract Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms. Significant correlations were identified between specific AABs and symptoms such as fever, muscle aches, anosmia, and dysgeusia. Notably, anti-AGTR1 antibodies, which contribute to endothelial glycocalyx (eGC) degradation, a process reversed by losartan, have emerged as strong predictors of core symptoms. AAB levels increased with symptom accumulation, peaking in patients exhibiting all four key symptoms. These findings highlight the role of AABs, particularly anti-AGTR1 antibodies, in determining symptom severity and suggest their involvement in the pathophysiology of COVID-19, including vascular complications. |
| format | Article |
| id | doaj-art-0487a02a7c044f4aa3d97df830b232e1 |
| institution | Kabale University |
| issn | 2056-7189 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Systems Biology and Applications |
| spelling | doaj-art-0487a02a7c044f4aa3d97df830b232e12025-01-19T12:28:15ZengNature Portfolionpj Systems Biology and Applications2056-71892025-01-0111111310.1038/s41540-025-00488-zDysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptomsDennyson Leandro M. Fonseca0Maj Jäpel1Michael Adu Gyamfi2Igor Salerno Filgueiras3Gabriela Crispim Baiochi4Yuri Ostrinski5Gilad Halpert6Yael Bublil Lavi7Elroy Vojdani8Thayna Silva-Sousa9Júlia Nakanishi Usuda10Juan Carlo Santos e Silva11Paula P. Freire12Adriel Leal Nóbile13Anny Silva Adri14Pedro Marçal Barcelos15Yohan Lucas Gonçalves Corrêa16Fernando Yuri Nery do Vale17Letícia Oliveira Lopes18Solveig Lea Schmidt19Xiaoqing Wang20Carl Vahldieck21Benedikt Fels22Lena F. Schimke23Gustavo Cabral-Miranda24Mario Hiroyuki Hirata25Taj Ali AKhan26Yen-Rei A. Yu27Rodrigo JS Dalmolin28Howard Amital29Aristo Vojdani30Haroldo Dutra Dias31Helder Nakaya32Hans D. Ochs33Jonathan I. Silverberg34Jason Zimmerman35Israel Zyskind36Avi Z. Rosenberg37Kai Schulze-Forster38Harald Heidecke39Rusan Catar40Guido Moll41Alexander Hackel42Kristina Kusche-Vihrog43Yehuda Shoenfeld44Gabriela Riemekasten45Reza Akbarzadeh46Alexandre H. C. Marques47Otavio Cabral-Marques48BIH Center for Regenerative Therapies (BCRT), Julius Wolff Institute (JWI), and Berlin Institute of Health (BIH); all Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH)Department of Rheumatology and Clinical Immunology, University of LübeckDepartament of Nephrology and Internal Intensive Care Medicine, Charité University HospitalDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP)Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP)Institute of Microbiology and Virology, Riga Stradins UniversityThe Dina Recanati School of Medicine, Reichman UniversityScakler Faculty of Medicine, Tel Aviv UniversityRegenera Medical 11860 Wilshire Blvd., Ste. 301Nuclear and Energy Research Institute, IPEN-CNEN/SPDepartment of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Branderburg Theodor FontaneDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP)Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP)Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP)Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP)Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP)Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP)Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP)Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP)Department of Rheumatology and Clinical Immunology, University of LübeckPriority Area Chronic Lung Diseases, Research Center BorstelInstitute of Physiology, University of LübeckInstitute of Physiology, University of LübeckDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP)Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP)Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP)Institute of Pathology and Diagnostic Medicine, Khyber Medical UniversityUniversity of Colorado Anschutz Medical CampusBioinformatics Multidisciplinary Environment, Federal University of Rio Grande do NorteZabludowicz Center for Autoimmune Diseases, Sheba Medical CenterImmunosciences Laboratory, IncDepartment of Neuroscience, Institute of Biomedical Sciences, Federal University of Minas Gerais (UFMG)Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP)Department of Pediatrics, University of Washington School of Medicine, and Seattle Children’s Research InstituteSchool of Medicine and Health Sciences, George Washington UniversityMaimonides Medical CenterMaimonides Medical CenterDepartment of Pathology, Johns Hopkins UniversityCellTrend Gesellschaft mit beschränkter Haftung (GmbH)CellTrend Gesellschaft mit beschränkter Haftung (GmbH)Departament of Nephrology and Internal Intensive Care Medicine, Charité University HospitalBIH Center for Regenerative Therapies (BCRT), Julius Wolff Institute (JWI), and Berlin Institute of Health (BIH); all Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH)Department of Rheumatology and Clinical Immunology, University of LübeckInstitute of Physiology, University of LübeckThe Dina Recanati School of Medicine, Reichman UniversityDepartment of Rheumatology and Clinical Immunology, University of LübeckDepartment of Rheumatology and Clinical Immunology, University of LübeckBioinformatics Multidisciplinary Environment, Federal University of Rio Grande do NorteBIH Center for Regenerative Therapies (BCRT), Julius Wolff Institute (JWI), and Berlin Institute of Health (BIH); all Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH)Abstract Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms. Significant correlations were identified between specific AABs and symptoms such as fever, muscle aches, anosmia, and dysgeusia. Notably, anti-AGTR1 antibodies, which contribute to endothelial glycocalyx (eGC) degradation, a process reversed by losartan, have emerged as strong predictors of core symptoms. AAB levels increased with symptom accumulation, peaking in patients exhibiting all four key symptoms. These findings highlight the role of AABs, particularly anti-AGTR1 antibodies, in determining symptom severity and suggest their involvement in the pathophysiology of COVID-19, including vascular complications.https://doi.org/10.1038/s41540-025-00488-z |
| spellingShingle | Dennyson Leandro M. Fonseca Maj Jäpel Michael Adu Gyamfi Igor Salerno Filgueiras Gabriela Crispim Baiochi Yuri Ostrinski Gilad Halpert Yael Bublil Lavi Elroy Vojdani Thayna Silva-Sousa Júlia Nakanishi Usuda Juan Carlo Santos e Silva Paula P. Freire Adriel Leal Nóbile Anny Silva Adri Pedro Marçal Barcelos Yohan Lucas Gonçalves Corrêa Fernando Yuri Nery do Vale Letícia Oliveira Lopes Solveig Lea Schmidt Xiaoqing Wang Carl Vahldieck Benedikt Fels Lena F. Schimke Gustavo Cabral-Miranda Mario Hiroyuki Hirata Taj Ali AKhan Yen-Rei A. Yu Rodrigo JS Dalmolin Howard Amital Aristo Vojdani Haroldo Dutra Dias Helder Nakaya Hans D. Ochs Jonathan I. Silverberg Jason Zimmerman Israel Zyskind Avi Z. Rosenberg Kai Schulze-Forster Harald Heidecke Rusan Catar Guido Moll Alexander Hackel Kristina Kusche-Vihrog Yehuda Shoenfeld Gabriela Riemekasten Reza Akbarzadeh Alexandre H. C. Marques Otavio Cabral-Marques Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms npj Systems Biology and Applications |
| title | Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms |
| title_full | Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms |
| title_fullStr | Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms |
| title_full_unstemmed | Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms |
| title_short | Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms |
| title_sort | dysregulated autoantibodies targeting agtr1 are associated with the accumulation of covid 19 symptoms |
| url | https://doi.org/10.1038/s41540-025-00488-z |
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