A new high throughput screening technique detected autoantibodies in COVID-19 patients that are specific for a wide variety of immunomodulatory extracellular and cell surface proteins, some of which have been linked to disease severity and clinical outcomes.
Several different dysfunctional immune responses have been linked to COVID-19, including the presence of anti-type I interferon autoantibodies. To broadly characterize autoantibodies in patients with COVID-19, Wang et al. used a new high-throughput multiplex detection technology they developed called Rapid Extracellular Antigen Profiling (REAP), which pans and binds serum IgG against a genetically encoded library of 2,770 human extracellular proteins presented on yeast cells a sequencing reading is quantified. Investigators examined 172 patients with COVID-19, 22 SARS-CoV-2 infected healthcare professionals (HCWs) with mild or asymptomatic infection, and 30 uninfected HCWs. They discovered that patients with COVID-19 had greater numbers of autoantibody reactivities compared to controls, and the highest scores occurred in patients with severe illness. Based on longitudinal REAP scoring of patients, it appeared that some of the autoantibodies existed before infection while others were newly acquired. It is striking that autoantibodies specific for cytokines, chemokines, growth factors, complement components and cell surface proteins, including anti-type I interferons, were elevated in patients with severe disease. In vitro function tests showed that some of these autoantibodies could inhibit the activity of the cytokines or chemokines they bound or increase FcR-dependent phagocytosis, and autoantibodies specific for various blood leukocyte surface proteins were at a reduced frequency of Connected cell types that express these proteins.
Using SARS-CoV-2 infected human ACE2 transgenic mice, Wang et al. showed that blocking antibodies against several of the cytokine targets of COVD-19-associated autoantibodies, including type 1 interferon, IL-18 receptor, IL-1β, IL-21, and GM-CSF, exacerbated the disease. Other autoantibodies against different tissue antigens have been associated with different clinical features and disease severity.
This study demonstrates the power of a new autoantibody screening technology and extends previous studies by showing that many different immunomodulatory autoantibodies are associated with severe COVID-19 disease. Further work is required to clarify the relative role of pre-existing versus post-infection-induced autoantibodies in disease pathogenesis. The analysis of autoantibodies associated with other viral infections is also of interest.
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