Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a letter
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article
Advertisement

ResearchIn-Press PreviewImmunology Open Access | 10.1172/jci.insight.147789

Aberrantly glycosylated IgG elicits pathogenic signaling in podocytes and signifies lupus nephritis

Rhea Bhargava,1 Sylvain Lehoux,2 Kayaho Maeda,1 Maria G. Tsokos,1 Suzanne Krishfield,1 Lena Y. Ellezian,1 Martin Pollak,1 Isaac E. Stillman,3 Richard D. Cummings,2 and George C. Tsokos1

1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

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

1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

Find articles by Lehoux, S. in: JCI | PubMed | Google Scholar |

1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

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

1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

Find articles by Tsokos, M. in: JCI | PubMed | Google Scholar |

1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

Find articles by Krishfield, S. in: JCI | PubMed | Google Scholar

1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

Find articles by Ellezian, L. in: JCI | PubMed | Google Scholar

1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

Find articles by Pollak, M. in: JCI | PubMed | Google Scholar

1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

Find articles by Stillman, I. in: JCI | PubMed | Google Scholar |

1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

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

1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

Find articles by Tsokos, G. in: JCI | PubMed | Google Scholar |

Published March 30, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.147789.
Copyright © 2021, Bhargava et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published March 30, 2021 - Version history
View PDF
Abstract

Lupus nephritis (LN) is a serious complication occurring in 50% of patients with systemic lupus erythematosus (SLE) for which there is lack of biomarkers, specific medications, and a clear understanding of its pathogenesis. The expression of calcium/calmodulin kinase IV (CaMK4) is increased in podocytes of patients with LN and lupus-prone mice and its podocyte-targeted inhibition averts the development of nephritis in mice. Nephrin is a key podocyte molecule essential for the maintenance of the glomerular slit diaphragm. Here, we show that the presence of fucose on N-glycans of IgG induces, whereas the presence of galactose ameliorates, podocyte injury through CaMK4 expression. Mechanistically, CaMK4 phosphorylates NFκB, upregulates the transcriptional repressor SNAIL, and limits the expression of nephrin. In addition, we demonstrate that increased expression of CaMK4 in biopsy specimens and in urine podocytes from people with LN is linked to active kidney disease. Our data shed new light on the role of IgG glycosylation in the development of podocyte injury and propose the development of ‘liquid kidney biopsy” approaches to diagnose LN.

Graphical Abstract
graphical abstract
Version history
  • Version 1 (March 30, 2021): In-Press Preview

Article tools

  • View PDF
  • Download citation information
  • Send a letter
  • 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 © 2021 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts