Abstract
A new high-throughput screening technique detected autoantibodies in COVID-19 patients specific for many different immunomodulatory extracellular and cell surface proteins, several of which were associated with disease severity and clinical outcomes.
Several different dysfunctional immune responses have been associated with COVID-19, including the presence of anti-type I interferon autoantibodies. In order to broadly characterize autoantibodies in patients with COVID-19, Wang et al. used a new high-throughput multiplexed detection technology they developed called Rapid Extracellular Antigen Profiling (REAP), in which serum IgG is panned against a genetically-barcoded library of 2770 human extracellular proteins displayed on yeast cells and binding is quantified by a sequencing readout. The investigators screened 172 patients with COVID-19, 22 SARS-CoV-2тАУinfected healthcare workers (HCWs) with mild or asymptomatic infection, and 30 uninfected HCWs. They discovered that the patients with COVID-19 had a greater number of autoantibody reactivities compared with controls, and the highest scoring was in patients with severe disease. Based on longitudinal REAP scoring of patients, it appeared that some of the autoantibodies were preexisting before infection, whereas others were newly acquired. Strikingly, autoantibodies specific for cytokines, chemokines, growth factors, complement components, and cell surface proteins were elevated in patients with severe disease, including anti-type I interferons. In vitro functional assays showed that some of these autoantibodies could inhibit the activity of the cytokines or chemokines that they bound, or enhance FcR-dependent phagocytosis, and autoantibodies specific for different blood leukocyte surface proteins were associated with decreased frequency of the cell types expressing those proteins.
Using SARS-CoV-2тАУinfected human ACE2 transgenic mice, Wang et al. showed that blocking antibodies to several of the cytokine targets of the COVD-19тАУassociated autoantibodies, including type 1 interferon, IL-18 receptor, IL-1╬▓, IL-21, and GM-CSF, exacerbated disease. Other autoantibodies against various tissue antigens were associated with different clinical features and disease severity.
This study demonstrates the power of a new autoantibody screening technology and expands on previous studies by showing that many different immunomodulatory autoantibodies are associated with severe COVID-19 disease. Further work will be needed to sort out the relative role of preexisting versus post-infection induced autoantibodies in disease pathogenesis. Also of interest will be the analysis of autoantibodies associated with other viral infections.
- Copyright ┬й 2021, American Association for the Advancement of Science
