Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI119616

A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease.

J Wu, J C Edberg, P B Redecha, V Bansal, P M Guyre, K Coleman, J E Salmon, and R P Kimberly

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Find articles by Wu, J. in: JCI | PubMed | Google Scholar

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Find articles by Edberg, J. in: JCI | PubMed | Google Scholar

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Find articles by Redecha, P. in: JCI | PubMed | Google Scholar

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Find articles by Bansal, V. in: JCI | PubMed | Google Scholar

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Find articles by Guyre, P. in: JCI | PubMed | Google Scholar

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Find articles by Coleman, K. in: JCI | PubMed | Google Scholar

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Find articles by Salmon, J. in: JCI | PubMed | Google Scholar

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Find articles by Kimberly, R. in: JCI | PubMed | Google Scholar

Published September 1, 1997 - More info

Published in Volume 100, Issue 5 on September 1, 1997
J Clin Invest. 1997;100(5):1059–1070. https://doi.org/10.1172/JCI119616.
© 1997 The American Society for Clinical Investigation
Published September 1, 1997 - Version history
View PDF
Abstract

A novel polymorphism in the extracellular domain 2 (EC2) of FcgammaRIIIA affects ligand binding by natural killer (NK) cells and monocytes from genotyped homozygous normal donors independently of receptor expression. The nonconservative T to G substitution at nucleotide 559 predicts a change of phenylalanine (F) to valine (V) at amino acid position 176. Compared with F/F homozygotes, FcgammaRIIIa expressed on NK cells and monocytes in V/V homozygotes bound more IgG1 and IgG3 despite identical levels of receptor expression. In response to a standard aggregated human IgG stimulus, FcgammaRIIIa engagement on NK cells from V/V (high-binding) homozygotes led to a larger rise in [Ca2+]i, a greater level of NK cell activation, and a more rapid induction of activation-induced cell death (by apoptosis). Investigation of an independently phenotyped normal cohort revealed that all donors with a low binding phenotype are F/F homozygotes, while all phenotypic high binding donors have at least one V allele. Initial analysis of 200 patients with SLE indicates a strong association of the low binding phenotype with disease, especially in patients with nephritis who have an underrepresentation of the homozygous high binding phenotype. Thus, the FcgammaRIIIa polymorphism at residue 176 appears to impact directly on human biology, an effect which may extend beyond autoimmune disease characterized by immune complexes to host defense mechanisms.

Version history
  • Version 1 (September 1, 1997): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts