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IgG4 serum levels are not elevated in cases of Post-COVID syndrome

Abel, J.; Walter, A. J.; Glueck, V.; Magnus, C. L.; Glueck, T.; Schuster, P.; Blaas, S.; Montanari, I.; Koller, M.; Mohr, A.; Hinterberger, T.; Salzberger, B.; Renner, K.; Mack, M.; Bals, R.; Schmidt, T.; Klemis, V.; Sester, M.; Kardashi, R.; de With, K.; Loew, T. H.; Malfertheiner, M.; Pfeifer, M.; Gessner, A.; Schmidt, B.; Schmalenberger, D.; Peterhoff, D.

2023-03-01 immunology
10.1101/2023.03.01.530454 bioRxiv
Show abstract

Recently, unexpectedly high virus-specific IgG4 levels were reported after more than two mRNA vaccinations. Class switch towards IgG4 occurs after long-term antigen exposure, downregulates immune responses and is associated with several autoimmune diseases. Here, we examined differences in antigen-specific IgG subtypes in serum samples from 64 Post-COVID patients and an equally sized cohort of convalescent controls. In both cohorts, the relative amounts of spike protein-specific IgG subtypes were comparable. IgG1 was the most frequent, followed by IgG3, IgG2, and IgG4. A difference between cohorts was observed only for IgG2, which was significantly lower in the Post-COVID cohort. Further analysis of the reactive IgG4 revealed a small but significant difference for the spike protein receptor-binding domain but not for the spike ectodomain. Since the total IgG4 levels are very low, we do not expect a biologically relevant role in Post-COVID syndrome. However, reduced virus-specific IgG2 levels could contribute to the persistence of SARS-CoV-2, causing chronic inflammation in the setting of Post-COVID syndrome.

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