Anti-PEG syndrome: the impact of biotechnology on immunothrombosis

Anti-PEG syndrome is an immunothrombotic adverse event characterized by complement activation and mediated by anti-PEG antibodies, which are typically generated through prior exposure to pharmaceutical formulations containing polyethoxylated compounds such as polyethylene glycol (PEG), polysorbates, and others. Its current relevance lies in the high prevalence of anti-PEG antibodies in the population, driven by the rise of biotechnology, and in the fact that these antibodies exhibit a dual nature of reactivity: Synthetic Reactivity: Anti-PEG antibodies can interact with the polyethoxylated structures of the widely used chemical compounds that induce their production, leading to various thrombotic adverse effects. Biological Reactivity: Anti-PEG antibodies can cross-react with mannosylated glycoproteins on the surface of various microorganisms, leading to severe COVID-19 and other forms of infectious immunothrombosis. Anti-PEG syndrome can manifest across a wide range of time after the initial antigen exposure, which may complicate the identification of its immunological etiology.