Neonatal Fc receptor in human immunity: Function and role in therapeutic intervention - 05/09/20
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Abstract |
The humoral immune response provides specific, long-lived protection against invading pathogens, via immunoglobulin production and other memory functions. IgG, the most abundant immunoglobulin isotype, has the longest half-life and protects against bacterial and viral infections. The neonatal Fc receptor (FcRn) transports IgG across barriers, for example, the placenta, enhancing fetal humoral immunity to levels similar to their mothers’. Importantly, FcRn, by protecting IgG from intracellular degradation, results in an approximately 21-day circulating IgG half-life and high plasma levels; similarly, FcRn recycles albumin and is the portal of entry for enteric cytopathic human orphan (echo) virus infection. Dysregulated immune responses may lead to antibodies against self-antigens (autoantibodies), resulting in organ-specific or systemic autoimmune diseases. Autoantibody-mediated diseases have been treated by nonspecific immunoglobulin-lowering/modulating therapies, including immunoadsorption, plasma exchange, and high-dose intravenous immunoglobulin. However, targeting FcRn with specific inhibitors results in reduction in only IgG levels. The effectiveness of FcRn inhibitors in autoimmune diseases, including myasthenia gravis and immune thrombocytopenia, provides further evidence that IgG is a primary driver in these autoantibody-mediated diseases. We describe the role of FcRn in human biology, including insights that clinical testing of FcRn inhibitors have provided into FcRn biology and autoimmune disease mechanisms, allowing fact-based speculation on their therapeutic potential.
Il testo completo di questo articolo è disponibile in PDF.Key words : Immunoglobulin, IgG, IgG lowering, autoimmune disease, FcRn inhibitors, plasma exchange, echovirus, half-life, IVIg
Abbreviations used : β2-m, CIDP, echo, Fc, FcRn, FcγR, IA, IC, IgG-IC, ITP, IVIg, MG, PLEX, PF, PV, SC, VNTR
Mappa
This article was written by the authors with editorial support provided by Laura Griffin, PhD, of iMed Comms, an Ashfield Company, part of UDG Healthcare plc, funded by UCB Pharma in accordance with Good Publications Practice (GPP3) guidelines (gpp3). The article was reviewed and approved for publication by all authors and the sponsor. The authors acknowledge Linda Feighery, PhD, CMPP, and Veronica Porkess, PhD, CMPP, of UCB Pharma for publication and editorial support. |
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Disclosure of potential conflict of interest: D.D. Patel is an employee of UCB Pharma and holds stock and/or stock options in UCB Pharma and Novartis. UCB Pharma is the manufacturer and sponsor of rozanolixizumab, an FcRn inhibitor, which is currently being investigated in clinical trials in a range of autoimmune disorders. J. B. Bussel has received consultancy fees from Amgen, Argenx, Dova (Sobi), Kezar, Momenta, Novartis, Regeneron, Rigel, UCB Pharma, and 3SBio. Argenx, Momenta, and UCB Pharma are all companies manufacturing and undertaking clinical development of FcRn inhibitors (efgartigimod, nipocalimab, and rozanolixizumab, respectively) discussed in this article. |
Vol 146 - N° 3
P. 467-478 - Settembre 2020 Ritorno al numeroBenvenuto su EM|consulte, il riferimento dei professionisti della salute.
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