Human amniotic IgA inhibits natural IgG autoantibodies of maternal or unrelated origin

We show that the natural autoantibody activity of amniotic IgG dramatically increases after purification, and that the IgG-depleted fraction can suppr ess the activity of IgG natural antibodies from amniotic fluid or from the maternal serum. This suppression is also observed towards serum IgG from un related adults but does not impair the tetanus antitoxin activity of serum- derived IgG. Absorption experiments and immunoglobulin separation by gel pe rmeation demonstrate that this suppression is due to monomeric immunoglobul ins of the IgA isotype. The inhibition is associated with an anti-F(ab(t))( 2) activity of the amniotic IgA, involving hypervariable regions of the IgG as demonstrated by different reactivities towards monoclonal IgG sharing t he same family of V-H and V-kappa domains. These results indicate that the inhibition of natural autoantibodies not only occurs with fetal and adult s erum IgM, as reported by other groups, but also with amniotic IgA, suggesti ng a general and important phenomenon. In the case of the amniotic fluid, I gA could protect the fetus against maternal IgG autoantibodies without inte rfering with simultaneously translocated antigen-induced IgG antibodies to pathogens.