RESUMEN
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.
Asunto(s)
Autoanticuerpos/inmunología , COVID-19/inmunología , Receptores Acoplados a Proteínas G/inmunología , Sistema Renina-Angiotensina/inmunología , Autoanticuerpos/sangre , Autoinmunidad , Biomarcadores/sangre , COVID-19/sangre , COVID-19/clasificación , Estudios Transversales , Femenino , Humanos , Aprendizaje Automático , Masculino , Análisis Multivariante , Receptor de Angiotensina Tipo 1/inmunología , Receptores CXCR3/inmunología , SARS-CoV-2 , Índice de Severidad de la EnfermedadRESUMEN
The current pandemic of coronavirus disease (COVID-19) caused by SARS-CoV-2 is a significant global health challenge. A recent study by Carvelli and colleagues now demonstrates the involvement of complement C5a and its receptor C5aR1 in disease progression and suggests that blockade of the C5a-C5aR1 axis may represent a potential therapeutic strategy against COVID-19.
Asunto(s)
Betacoronavirus/inmunología , Complemento C5a/inmunología , Infecciones por Coronavirus/inmunología , Neumonía Viral/inmunología , Receptor de Anafilatoxina C5a/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Betacoronavirus/efectos de los fármacos , Betacoronavirus/fisiología , COVID-19 , Complemento C5a/metabolismo , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/virología , Modelos Animales de Enfermedad , Humanos , Pandemias , Neumonía Viral/terapia , Neumonía Viral/virología , Receptor de Anafilatoxina C5a/metabolismo , Receptores Acoplados a Proteínas G/inmunología , Receptores Acoplados a Proteínas G/metabolismo , SARS-CoV-2 , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunologíaRESUMEN
INTRODUCTION: G protein-coupled receptors (GPCRs) play key roles in many biological functions and are linked to many diseases across all therapeutic areas. As such, GPCRs represent a significant opportunity for antibody-based therapeutics. AREAS COVERED: The structure of the major GPCR families is summarized in the context of choice of antigen source employed in the drug discovery process and receptor biology considerations which may impact on targeting strategies. An overview of the therapeutic GPCR-antibody target landscape and the diversity of current therapeutic programs is provided along with summary case studies for marketed antibody drugs or those in advanced clinical studies. Antibodies in early clinical studies and the emergence of next-generation modalities are also highlighted. EXPERT OPINION: The GPCR-antibody pipeline has progressed significantly with a number of technical developments enabling the successful resolution of some of the challenges previously encountered and this has contributed to the growing interest in antibody-based therapeutics addressing this target class.