Nature Communications (Oct 2022)

The Fab region of IgG impairs the internalization pathway of FcRn upon Fc engagement

  • Maximilian Brinkhaus,
  • Erwin Pannecoucke,
  • Elvera J. van der Kooi,
  • Arthur E. H. Bentlage,
  • Ninotska I. L. Derksen,
  • Julie Andries,
  • Bianca Balbino,
  • Magdalena Sips,
  • Peter Ulrichts,
  • Peter Verheesen,
  • Hans de Haard,
  • Theo Rispens,
  • Savvas N. Savvides,
  • Gestur Vidarsson

DOI
https://doi.org/10.1038/s41467-022-33764-1
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 14

Abstract

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Disrupting the association between the Immunoglobulin G constant fragment (Fc) and the neonatal Fc receptor (FcRn) by engineered antibodies is a promising strategy to reduce autoantibody levels in autoimmune diseases. Here authors show that the variable fragment (Fab) of immunoglobulins could disturb the Fc-FcRn interaction, therefore the therapeutic effect of Fc-only fragments might surpass that of Fc-engineered antibodies with enhanced binding to FcRn.