Frontiers in Immunology (Sep 2022)
Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity
- Franziska Sotzny,
- Igor Salerno Filgueiras,
- Claudia Kedor,
- Helma Freitag,
- Kirsten Wittke,
- Sandra Bauer,
- Nuno Sepúlveda,
- Nuno Sepúlveda,
- Dennyson Leandro Mathias da Fonseca,
- Gabriela Crispim Baiocchi,
- Alexandre H. C. Marques,
- Myungjin Kim,
- Tanja Lange,
- Desirée Rodrigues Plaça,
- Finn Luebber,
- Finn Luebber,
- Frieder M. Paulus,
- Roberta De Vito,
- Igor Jurisica,
- Igor Jurisica,
- Igor Jurisica,
- Igor Jurisica,
- Igor Jurisica,
- Kai Schulze-Forster,
- Friedemann Paul,
- Friedemann Paul,
- Friedemann Paul,
- Friedemann Paul,
- Judith Bellmann-Strobl,
- Judith Bellmann-Strobl,
- Judith Bellmann-Strobl,
- Judith Bellmann-Strobl,
- Rebekka Rust,
- Rebekka Rust,
- Rebekka Rust,
- Rebekka Rust,
- Uta Hoppmann,
- Uta Hoppmann,
- Uta Hoppmann,
- Uta Hoppmann,
- Yehuda Shoenfeld,
- Yehuda Shoenfeld,
- Gabriela Riemekasten,
- Harald Heidecke,
- Otavio Cabral-Marques,
- Otavio Cabral-Marques,
- Otavio Cabral-Marques,
- Otavio Cabral-Marques,
- Otavio Cabral-Marques,
- Carmen Scheibenbogen
Affiliations
- Franziska Sotzny
- Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Igor Salerno Filgueiras
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Claudia Kedor
- Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Helma Freitag
- Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Kirsten Wittke
- Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Sandra Bauer
- Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Nuno Sepúlveda
- Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland
- Nuno Sepúlveda
- CEAUL – Centro de Estatística e Aplicações da Universidade de Lisboa, Lisbon, Portugal
- Dennyson Leandro Mathias da Fonseca
- Interunit PostGraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo, Sao Paulo, Brazil
- Gabriela Crispim Baiocchi
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Alexandre H. C. Marques
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Myungjin Kim
- Data Science Initiative, Brown University, Providence, RI, United States
- Tanja Lange
- Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
- Desirée Rodrigues Plaça
- Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Finn Luebber
- Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
- Finn Luebber
- Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany
- Frieder M. Paulus
- Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany
- Roberta De Vito
- 0Department of Biostatistics and the Data Science Initiative, Brown University, Providence, RI, United States
- Igor Jurisica
- 1Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada
- Igor Jurisica
- 2Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON, Canada
- Igor Jurisica
- 3Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- Igor Jurisica
- 4Department of Computer Science, University of Toronto, Toronto, ON, Canada
- Igor Jurisica
- 5Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia
- Kai Schulze-Forster
- 6CellTrend GmbH, Luckenwalde, Germany
- Friedemann Paul
- 7Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany
- Friedemann Paul
- 8Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Berlin, Germany
- Friedemann Paul
- 9Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Friedemann Paul
- 0NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Judith Bellmann-Strobl
- Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Judith Bellmann-Strobl
- 7Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany
- Judith Bellmann-Strobl
- 8Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Berlin, Germany
- Judith Bellmann-Strobl
- 9Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Rebekka Rust
- Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Rebekka Rust
- 7Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany
- Rebekka Rust
- 8Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Berlin, Germany
- Rebekka Rust
- 9Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Uta Hoppmann
- Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Uta Hoppmann
- 7Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany
- Uta Hoppmann
- 8Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Berlin, Germany
- Uta Hoppmann
- 9Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Yehuda Shoenfeld
- 1Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Hashomer, Israel
- Yehuda Shoenfeld
- 2Ariel University, Ariel, Israel
- Gabriela Riemekasten
- Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
- Harald Heidecke
- 6CellTrend GmbH, Luckenwalde, Germany
- Otavio Cabral-Marques
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Otavio Cabral-Marques
- Interunit PostGraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo, Sao Paulo, Brazil
- Otavio Cabral-Marques
- Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Otavio Cabral-Marques
- 3Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sao Paulo, Brazil
- Otavio Cabral-Marques
- 4Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, RN, Brazil
- Carmen Scheibenbogen
- Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- DOI
- https://doi.org/10.3389/fimmu.2022.981532
- Journal volume & issue
-
Vol. 13
Abstract
Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels targeting several G-protein coupled receptors (GPCR). In this exploratory study, we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and asymptomatic post COVID-19 controls (n=40) were also included in the study as control groups. We found lower levels for various AABs in PCS compared to at least one control group, accompanied by alterations in the correlations among AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1, and ADRA2A as the strongest classifiers (AABs stratifying patients according to disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms were associated with ADRB2 AAB levels in PCS/ME/CFS patients. Our study identified dysregulation of AAB against various receptors involved in the autonomous nervous system (ANS), vaso-, and immunoregulation and their correlation with symptom severity, pointing to their role in the pathogenesis of PCS.
Keywords
- autoantibodies
- COVID-19
- post COVID syndrome
- Chronic Fatigue Syndrome
- ME/CFS,
- G-protein coupled receptor