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

Abstract

We show that the natural autoantibody activity of amniotic IgG dramatically increases after purification, and that the IgG-depleted fraction can suppress the activity of IgG natural antibodies from amniotic fluid or from the maternal serum. This suppression is also observed towards serum IgG from unrelated adults but does not impair the tetanus antitoxin activity of serum-derived IgG. Absorption experiments and immunoglobulin separation by gel permeation demonstrate that this suppression is due to monomeric immunoglobulins of the IgA isotype. The inhibition is associated with an anti-F(ab')2 activity of the amniotic IgA, involving hypervariable regions of the IgG as demonstrated by different reactivities towards monoclonal IgG sharing the same family of VH and Vkappa domains. These results indicate that the inhibition of natural autoantibodies not only occurs with fetal and adult serum IgM, as reported by other groups, but also with amniotic IgA, suggesting a general and important phenomenon. In the case of the amniotic fluid, IgA could protect the fetus against maternal IgG autoantibodies without interfering with simultaneously translocated antigen-induced IgG antibodies to pathogens.

Antibody Repertoire Development in Fetal And Neonatal Piglets. IV. Switch Recombination, Primarily in Fetal Thymus, Occurs Independent of Environmental Antigen and Is Only Weakly Associated with Repertoire Diversification

“…Because the GC reaction occurs in response to stimulation with Tdependent Ags, switch would not be expected to occur in an environment free of T-dependent environmental Ags. Nevertheless, there are reports of IgA present as early as the second trimester in human fetuses (13)(14)(15). IgA-containing cells have been reported to be present in 180-day fetuses (16), and transcripts can be detected on day 110 (17).…”

Complex immune correlates of protection in HIV‐1 vaccine efficacy trials

“…Moreover, the IgA/IgG ratio for some HIV‐1 envelope glycoproteins correlated with increased infection risk (OR=1.58 to 1.79, P‐value <.01 to <.001) . At the time, this type of interference of IgG function was only previously reported for host immunity to bacteria, the regulation of autoantibodies and ADCC activity of EBV‐infected target cells in nasopharyngeal cancer . HIV‐1 Env IgA interference with IgG‐mediated effector function was subsequently confirmed in an HIV‐1 infection cohort study …”

Lectin-based analysis of fucose and sialic acid expressions on human amniotic IgA during normal pregnancy

“…In contrast to IgG, amniotic IgA of fetal origin is more in favor of a preimmune role by natural polyreactive IgA antibodies similar to that reported for secretion [20]. Moreover, IgA in amniotic fluid is involved in the protection of the fetus against maternal IgG autoantibodies [21]. According to Quan et al [18] the amniotic immunoglobulins, both IgG and IgA, can serve as a protection against pathogens and act through mechanisms similar to those observed in the female genital fluid.…”