Detection of PEG-specific antibodies in SARS-CoV-2 positive and negative sera with implications for autoimmune reactivity

Polyethylene glycol (PEG) is a stabilizing polymer that may act as an immunogen, as some individuals produce antibodies against it and its covalent attachment to active proteins. We wanted to determine if different titers of PEG antibodies are detected in sera from subjects before and after the SARS-CoV-2 pandemic peak, and if these antibodies possibly contribute to autoimmunity. Using ELISA, we measured IgG, IgM, IgA and IgE antibodies against different sizes of PEG, Moderna COVID-19 vaccine ingredients, and phosphatidylcholine in sera from 90 healthy adults purchased in 2018 that were negative for SARS-CoV-2 IgG antibody, and sera from 90 blood donors purchased in 2023 (collected mid-August 2023) that tested positive for SARS-CoV-2 IgG. To find possible reactivity with human tissue, we also applied both polyclonal and monoclonal antibodies raised in mouse/rabbit specifically against PEG-5K to 65 different human tissue antigens. Analysis of data showed that at 3SD above the mean of the negative control, significant elevations in IgG and IgM antibodies were detected against different sizes of PEG, vaccine ingredients, and phosphatidylcholine. For IgE, significant elevations were found in the PEG-specific antibodies. For IgA antibodies, significant elevation was found only against phosphatidylcholine. The application of monoclonal and polyclonal antibodies made against PEG to 65 different human tissue antigens showed reactions with 20 out of 65 different antigens for rabbit polyclonal, 7 out of 65 for rabbit monoclonal, and 6 out of 65 for mouse monoclonal anti-PEG antibody. Administration of PEGylated products may result in the production of PEG-specific antibodies that may contribute to autoimmunity.