Targeting FcRn for immunomodulation: Benefits, risks, and practical considerations

Hans Hartmut Peter, Hans D. Ochs, Charlotte Cunningham-Rundles, Donald C. Vinh, Peter Kiessling, Bernhard Greve, Stephen Jolles

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations


The neonatal fragment crystallizable (Fc) receptor (FcRn) functions as a recycling mechanism to prevent degradation and extend the half-life of IgG and albumin in the circulation. Several FcRn inhibitors selectively targeting IgG recycling are now moving rapidly toward clinical practice in neurology and hematology. These molecules accelerate the destruction of IgG, reducing pathogenic IgG and IgG immune complexes, with no anticipated effects on IgA, IgM, IgE, complement, plasma cells, B cells, or other cells of the innate or adaptive immune systems. FcRn inhibitors have potential for future use in a much wider variety of antibody-mediated autoimmune diseases. Given the imminent clinical use, potential for broader utility, and novel mechanism of action of FcRn inhibitors, here we review data from 4 main sources: (a) currently available activity, safety, and mechanism-of-action data from clinical trials of FcRn inhibitors; (b) other procedures and treatments that also remove IgG (plasma donation, plasma exchange, immunoadsorption); (c) diseases resulting in loss of IgG; and (d) primary immunodeficiencies with potential mechanistic similarities to those induced by FcRn inhibitors. These data have been evaluated to provide practical considerations for the assessment, monitoring, and reduction of any potential infection risk associated with FcRn inhibition, in addition to highlighting areas for future research.

Original languageEnglish
Pages (from-to)479-491.e5
JournalJournal of Allergy and Clinical Immunology
Issue number3
StatePublished - Sep 2020


  • FcRn
  • FcRn inhibitors
  • IgG
  • albumin
  • antibody-mediated autoimmunity
  • autoantibody
  • hypogammaglobulinemia
  • immunoglobulin
  • infection risk
  • neonatal Fc receptor


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