ResearchIn-Press PreviewImmunology
Open Access | 10.1172/jci.insight.147789
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
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Bhargava, R.
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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
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Lehoux, S.
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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
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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
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Tsokos, M.
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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
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1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America
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3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America
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1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America
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1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America
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3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America
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Stillman, I.
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1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America
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3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America
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1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America
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Published March 30, 2021 - More info
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.