Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity

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Cabral-Marques, Otavio ; Halpert, Gilad ; Schimke, Lena F. ; Ostrinski, Yuri ; Vojdani, Aristo ; Baiocchi, Gabriela Crispim ; Freire, Paula Paccielli ; Filgueiras, Igor Salerno ; Zyskind, Israel ; Lattin, Miriam T. ; Tran, Florian ; Schreiber, Stefan ; Marques, Alexandre H. C. ; Placa, Desiree Rodrigues ; Fonseca, Dennyson Leandro M. ; Humrich, Jens Y. ; Mueller, Antje ; Giil, Lasse M. ; Grasshoff, Hanna ; Schumann, Anja ; Hackel, Alexander ; Junker, Juliane ; Meyer, Carlotta ; Ochs, Hans D. ; Lavi, Yael Bublil ; Scheibenbogen, Carmen ; Dechend, Ralf ; Jurisica, Igor ; Schulze-Forster, Kai ; Silverberg, Jonathan, I ; Amital, Howard ; Zimmerman, Jason ; Heidecke, Harry ; Rosenberg, Avi Z. ; Riemekasten, Gabriela ; Shoenfeld, Yehuda

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 13, n. 1, p. 12-pg., 2022-03-09.

Abstract

COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. In order to understand the role of these immune globulins in the pathogenesis of the disease, it is important to explore the autoantibody spectra. Here we show, by a cross-sectional study of 246 individuals, that autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules associate with the clinical severity of COVID-19. Patients with moderate and severe disease are characterized by higher autoantibody levels than healthy controls and those with mild COVID-19 disease. Among the anti-GPCR autoantibodies, machine learning classification identifies the chemokine receptor CXCR3 and the RAS-related molecule AGTR1 as targets for antibodies with the strongest association to disease severity. Besides antibody levels, autoantibody network signatures are also changing in patients with intermediate or high disease severity. Although our current and previous studies identify anti-GPCR antibodies as natural components of human biology, their production is deregulated in COVID-19 and their level and pattern alterations might predict COVID-19 disease severity. COVID-19, similarly to systemic autoimmune diseases, is characterised by the presence of autoantibodies. Authors show here that the abundance and network signature of autoantibodies targeting G protein-coupled receptors and RAS-related proteins are altered in COVID-19 patients, and the level of disruption marks clinical severity. (AU)

• FAPESP's process: 20/07069-0 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
• Grantee: Otávio Cabral Marques
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/18886-9 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
• Grantee: Otávio Cabral Marques
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/16246-2 - Holistic characterization of T cell exhaustion in patients with Zika
• Grantee: Dennyson Leandro Mathias da Fonseca
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/11710-2 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with Dengue
• Grantee: Desirée Rodrigues Plaça
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/07972-1 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
• Grantee: Gabriela Crispim Baiocchi
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/09146-1 - Systemic and integrative analysis of molecular mechanisms associated with immunoregulation in patients with COVID-19
• Grantee: Paula Paccielli Freire-Barguil
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/01688-0 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
• Grantee: Otávio Cabral Marques
• Support Opportunities: Scholarships in Brazil - Young Researchers