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Cited by 288Monoclonal and Polyclonal Antibodies ResearchT-cell and B-cell ImmunologyImmunodeficiency and Autoimmune Disorders

The therapeutic age of the neonatal Fc receptor

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Pyzik, Michal, Kozicky, Lisa K., Gandhi, Amit K., Blumberg, Richard S.·2023·Nature Reviews Immunology
DOI 10.1038/s41577-022-00821-1PMC PMC9891766
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Abstract

IgGs are essential soluble components of the adaptive immune response that evolved to protect the body from infection. Compared with other immunoglobulins, the role of IgGs is distinguished and enhanced by their high circulating levels, long half-life and ability to transfer from mother to offspring, properties that are conferred by interactions with neonatal Fc receptor (FcRn). FcRn binds to the Fc portion of IgGs in a pH-dependent manner and protects them from intracellular degradation. It also allows their transport across polarized cells that separate tissue compartments, such as the endothelium and epithelium. Further, it is becoming apparent that FcRn functions to potentiate cellular immune responses when IgGs, bound to their antigens, form IgG immune complexes. Besides the protective role of IgG, IgG autoantibodies are associated with numerous pathological conditions. As such, FcRn blockade is a novel and effective strategy to reduce circulating levels of pathogenic IgG autoantibodies and curtail IgG-mediated diseases, with several FcRn-blocking strategies on the path to therapeutic use. Here, we describe the current state of knowledge of FcRn-IgG immunobiology, with an emphasis on the functional and pathological aspects, and an overview of FcRn-targeted therapy development.

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200 of 231 shown

Cited by

Sorted by citations

Authors
Pyzik, M., Kozicky, L. K., Gandhi, A. K., & Blumberg, R. S.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Blumberg, Richard S.
ORCID
Venue
Nature Reviews Immunology
Publisher
Springer Science and Business Media LLC
Published
2023-02-01
Volume
23
Issue
7
Pages
415-432
ISSN
  • 1474-1733 (ISSN-L)
  • 1474-1741
DOI
10.1038/s41577-022-00821-1
PMC
PMC9891766
OpenAlex
W4318767306
Cited by
288
References
8
Citations by year
2026: 100 · 2025: 100 · 2024: 75 · 2023: 13
FWCI
12.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature reviews. Immunology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (DK053056, DK034854)
  • Canadian Institutes of Health Research (DK034854)
  • Harvard Digestive Diseases Center, Harvard University (DK034854)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK034854, R01DK053056, DK053056, R56DK053056, P30DK034854)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
Keywords
neonatal Fc receptor, IgG, FcRn blockade, IgG autoantibodies, antibody-mediated autoimmunity, antibody recycling, transcytosis, IgG immune complexes, IgG half-life
MeSH terms
Antigens, Humans, Immunoglobulin G, Infant, Newborn, Receptors, Fc, Histocompatibility Antigens Class I

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