"Abstract
Repeated inoculation with messenger RNA (mRNA) vaccines elicits immunoglobulin G4 (IgG4) antibody production. Such an increase in the concentration of specific and non-specific IgG4 antibodies allows the growth of some types of cancer by blocking the activation of effector immune cells. This work proposes the hypothesis that cancer growth may be indirectly promoted by increased concentrations of non-specific IgG4 antibodies by the following mechanisms: 1) IgG4 antibodies can bind to anti-tumor IgG1 antibodies and block their interaction with receptors located on effector cells, thus preventing the destruction of cancer cells, 2) IgG4 can interact with fragment crystallizable gamma receptor IIb (FcγRIIB) inhibitory receptors, thus reducing effector functions of innate immune cells, and 3) targeting of specific epitopes by IgG4 could be oncogenic by inducing the production of a microenvironment that can promote cancer development. This article reviews the supporting literature and suggests several experimental protocols to evaluate this hypothesis in the context of repeated inoculation with mRNA vaccines. Additionally, this work proposes some management options aimed at reducing the unfavorable molecular consequences that could mediate cancer development when encountering high concentrations of IgG4 antibodies.
Introduction
... [A]fter the second mRNA vaccine injection, an unexpected long-term side effect has been observed worldwide: a switch in the isotype of IgG antibodies took place. Before the emergence of these observations in the general mRNA vaccinated population, this phenomenon appeared to have been documented in single individuals and described as a rare vaccine side effect; either producing IgG4-related disease (RD) or experiencing a relapse of IgG4-RD symptoms. The phenomenon of rising IgG4 antibodies post mRNA vaccination has now been documented in studies involving human participants and at least one animal study. It appears that the rate of increase of IgG4 antibodies can surpass all other IgG antibodies developed towards the spike protein, rising consistently from an average of 0.04% after the second immunization to 19.27% after the third one. This was echoed by another study, where the median level of IgG4 antibodies directed against the spike protein was 21.2% of all IgG antibodies. In stark contrast, this phenomenon has not been reported in non-vaccinated individuals.
Contributing factors to IgG4 expansion
Several investigations have now demonstrated that this response is only produced by the mRNA-based vaccines (Pfizer/BioNTech or Moderna); individuals who received adenoviral vector-based or protein-based vaccines did not generate such a rise in IgG4 concentrations...
Conclusions
... One condition of particular interest in the context of emerging mRNA vaccination side effects of increased IgG4 levels is the IgG4-RD, which also frequently presents with increased IgG4 levels. It has been proposed that longstanding IgG4-RD may progress to malignancy. A meta-analysis and systematic review of individuals with IgG4-RD found that standardized incidence ratios were significantly increased, i.e., 4-fold for pancreatic cancer and 69-fold for lymphoma. It is suggested that after the launch of the widespread COVID-19 immunization program involving mRNA injections, lymphoma is unquestionably the sentinel condition to be attentively observed at the population level...
IgG4 antibody levels seen in IgG4-RD would be an appropriate starting point to commence monitoring the developing situation. The IgG4 serum levels are one of the most frequent markers investigated, with levels from 1.35 mg/mL to 2.48 mg/mL of IgG4 proposed by different authors with 1.35 mg/mL value now recognized as part of the diagnostic criteria of IgG4-RD...
It is proposed that physicians start taking note of IgG4 levels in all their mRNA vaccinated patients."
© The Author(s) 2024.
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