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Nat Commun. 2015 Mar 31;6:6651. doi: 10.1038/ncomms7651.

Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss.

Author information

1
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
2
1] Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen 91054, Germany [2] Nikolaus Fiebiger Center of Molecular Medicine, University of Erlangen- Nuremberg, Erlangen 91054, Germany.
3
1] Department of Rheumatology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands [2] Center of Proteomics and Metabolomics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
4
Department of Chemistry and Pharmacy, Interdisciplinary Center for Molecular Materials (ICMM), University of Erlangen-Nuremberg, Erlangen 91054, Germany.
5
Rheumatology Unit, Department of Medicine, Karolinska Institute and Karolinska University Hospital, Solna 17177, Sweden.
6
Orgentec Diagnostika, Mainz 55129, Germany.
7
Department of Genetics, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
8
Department of Rheumatology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.

Abstract

Immunglobulin G (IgG) sialylation represents a key checkpoint that determines the engagement of pro- or anti-inflammatory Fcγ receptors (FcγR) and the direction of the immune response. Whether IgG sialylation influences osteoclast differentiation and subsequently bone architecture has not been determined yet, but may represent an important link between immune activation and bone loss. Here we demonstrate that desialylated, but not sialylated, immune complexes enhance osteoclastogenesis in vitro and in vivo. Furthermore, we find that the Fc sialylation state of random IgG and specific IgG autoantibodies determines bone architecture in patients with rheumatoid arthritis. In accordance with these findings, mice treated with the sialic acid precursor N-acetylmannosamine (ManNAc), which results in increased IgG sialylation, are less susceptible to inflammatory bone loss. Taken together, our findings provide a novel mechanism by which immune responses influence the human skeleton and an innovative treatment approach to inhibit immune-mediated bone loss.

PMID:
25825024
PMCID:
PMC4389255
DOI:
10.1038/ncomms7651
[Indexed for MEDLINE]
Free PMC Article

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