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

Autor(es):Mostrar menos -

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

• Tipo de documento: Artigo Científico
• Fonte: NATURE COMMUNICATIONS; v. 13, n. 1, p. 12-pg., 2022-03-09.

Resumo

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)

• Processo FAPESP: 20/07069-0 - Análise sistêmica e integrativa dos mecanismos de exaustão dos linfócitos T de pacientes com COVID-19
• Beneficiário: Otávio Cabral Marques
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/18886-9 - Análise sistêmica e integrativa da resposta imune às infecções virais por Zika e Dengue
• Beneficiário: Otávio Cabral Marques
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 20/16246-2 - Caracterização holística do mecanismo de exaustão dos linfócitos T em pacientes com Zika
• Beneficiário: Dennyson Leandro Mathias da Fonseca
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 20/11710-2 - Análise sistêmica e integrativa dos mecanismos de exaustão dos linfócitos T de pacientes com Dengue
• Beneficiário: Desirée Rodrigues Plaça
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 20/07972-1 - Análise sistêmica e integrativa dos mecanismos de exaustão dos linfócitos T de pacientes com COVID-19
• Beneficiário: Gabriela Crispim Baiocchi
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 20/09146-1 - Análise sistêmica e integrativa dos mecanismos moleculares associados à imunorregulação em pacientes com COVID-19
• Beneficiário: Paula Paccielli Freire-Barguil
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 20/01688-0 - Análise sistêmica e integrativa da resposta imune às infecções virais por Zika e Dengue
• Beneficiário: Otávio Cabral Marques
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores