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.
Highlights
COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases
We assessed the concentrations of autoantibodies against G protein-coupled receptors (GPCR) involved in chemotaxis and inflammation (CXCR323,24 and C5AR125), coagulation (F2R26), and neuronal receptors (ADRA1A, ADRB1, and ADRB2, CHRMs)[27–31], which have been implicated in the development of COVID-19 disease
We explored the potential presence of autoantibodies against STAB1 (STAB1-aab), a scavenger receptor, as a potential new candidate in COVID-19 pathology since, despite the lack of investigations into its role in COVID-19, its multifunctionality during leukocyte trafficking, tissue homeostasis, and resolution of inflammation suggests that it could be relevant for disease severity[33,34]
Summary
COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. While patients with mild disease or asymptomatic infection exhibit increased autoantibody reactivity relative to uninfected individuals, those with severe disease have the highest reactivity scores These results are in line with our previous report[13] on autoantibodies targeting the largest superfamily of integral membrane proteins in humans[14], i.e., G protein-coupled receptors (GPCR), suggesting that these autoantibodies are natural components of human biology that become dysregulated in autoimmune diseases[15]. Recent studies have detected functional antibodies against GPCRs in the sera of patients with COVID-19 and have indicated that they may be associated with disease severity[16–18] These investigations focused only on a few anti-GPCR autoantibodies. We employ a systems immunology approach (Fig. 1a) to characterize the relationship between autoantibodies targeting a broad group of GPCRs and RAS-related molecules with COVID-19 severity by determining their correlation signatures across SARS-CoV-2infected patients versus healthy individuals
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
