HFcRn-mediated transplacental immunoglobulin G transport: protection of and threat to the human fetus and newborn.
In human newborns, endogenous levels of plasma immunoglobulin G (IgG) begin to rise slowly after birth following exposure to the environment. For immunoprotection during fetal and early neonatal life, maternal IgG is provided by transplacental transport. While cellular immunoprotective IgG effects are mainly triggered by FcγRI, -RII and -RIII, transplacental IgG transfer is mediated by the MHC class I-like neonatal Fc-receptor, hFcRn. This compact review explains the mechanism of hFcRn-mediated IgG transcytosis across the placental barrier - syncytiotrophoblast and fetal endothelial cells. Restrictions of this IgG transport are summarized. These include IgG subclass discrimination and limited IgG transport before the third trimester that can cause insufficient protection from infections of preterm (≤ 35 th week) delivered babies. As hFcRn does not discriminate beneficial from hazardous IgGs, maternal auto- and alloimmune as well as therapeutic antibodies can reach the fetus. The consequences including severe diseases of the newborn are summarized in this article.
Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria. isabella.ellinger@meduniwien.ac.at
Isabella
I
Ellinger
Renate
R
Fuchs
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D007112:Immunity, Maternally-Acquired / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D011247:Pregnancy; D011961:Receptors, Fc / Q000502:physiology*; D057900:Transcytosis / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D007518:Isoantibodies; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; C100688:Fc receptor, neonatal