Comparison of IgG4 and asymmetric IgG and their similar properties as blocking antibodies

Blocking antibody can inhibit immunoreactions. IgG4 and asymmetric (asym) IgG are both referred to as "blocking antibodies". However, their working mechanisms and effects on maternal-fetal immune tolerance in pregnancy remain unclear.

To explore the relationship between IgG4 and asym IgG as well as IgG4's role in maternal-fetal immune tolerance, Western blot, immunohistochemistry, protein array, and immune turbidimetric assay were employed to compare the structural and functional properties of the two antibodies. These included their distribution, density, and concentration in maternal sera as well as their interactions with other IgG subtypes.

Significant molecular structural overlap was found between IgG4 and asym IgG. IgG4 exhibited an asym Fab glycosylated pattern. Both IgG4 and asym IgG, unlike symmetric(sym) IgG or IgG1, bound to cross-species IgGs. IgG1 and IgG4 were distributed in the outer layer of placental villi and within the lumens of placental intravascular vessels. In early placental villi, they were localized in the syncytiotrophoblast layer, while in the decidua, there were found mainly in lymphocytes. IgG4 exhibited Fc-Fc interactions with IgG1, which were enhanced by glutathione (GSH) in a dose - dependent manner. IgG4 levels increased in early pregnancy sera but reduced during the late phase, likely contributing to placental immune tolerance early in pregnancy.

The study indicates that IgG4 and asym IgG are likely the same molecule with different purity but with similar biological properties. The IgG4 Fc-Fc interaction may be a key mechanism for immunotolerance in reproduction helping to establish immune equilibrium between mother and fetus during pregnancy.