We propose ‘anti-PEG syndrome’ as a candidate immunothrombotic adverse event, involving complement activation and mediated by anti-PEG antibodies, 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, a candidate contributor to various thrombotic adverse effects. Pattern-Mimicry Reactivity: Anti-PEG antibodies could, through structural rather than sequence specific recognition, bind phospholipid surfaces exposed by tissue damage from respiratory infections and other insults — a hypothesis proposed here as a candidate amplifier of thromboinflammatory events, pending direct experimental confirmation with naturally circulating human antibodies. 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. Both the drug-attribution component (Section 6) and the anti-PEG pattern-mimicry hypothesis (Section 7) are presented here as testable proposals rather than established mechanisms; the evidentiary basis and limitations of each are made explicit throughout.
Añaños et al. (Thu,) studied this question.