Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss

Ulrike Harre, Stefanie C. Lang, René Pfeifle, Yoann Rombouts, Sabine Frühbeißer, Khaled Amara, Holger Bang, Anja Lux, Carolien A. Koeleman, Wolfgang Baum, Katharina Dietel, Franziska Gröhn, Vivianne Malmström, Lars Klareskog, Gerhard Krönke, Roland Kocijan, Falk Nimmerjahn, René E. M. Toes, Martin Herrmann, Hans Ulrich Scherer and Georg Schett ()
Additional contact information
Ulrike Harre: University of Erlangen-Nuremberg
Stefanie C. Lang: University of Erlangen-Nuremberg
René Pfeifle: University of Erlangen-Nuremberg
Yoann Rombouts: Leiden University Medical Center
Sabine Frühbeißer: Interdisciplinary Center for Molecular Materials (ICMM), University of Erlangen-Nuremberg
Khaled Amara: Rheumatology Unit, Karolinska Institute and Karolinska University Hospital
Holger Bang: Orgentec Diagnostika
Anja Lux: University of Erlangen-Nuremberg
Carolien A. Koeleman: Leiden University Medical Center
Wolfgang Baum: University of Erlangen-Nuremberg
Katharina Dietel: University of Erlangen-Nuremberg
Franziska Gröhn: Interdisciplinary Center for Molecular Materials (ICMM), University of Erlangen-Nuremberg
Vivianne Malmström: Rheumatology Unit, Karolinska Institute and Karolinska University Hospital
Lars Klareskog: Rheumatology Unit, Karolinska Institute and Karolinska University Hospital
Gerhard Krönke: University of Erlangen-Nuremberg
Roland Kocijan: University of Erlangen-Nuremberg
Falk Nimmerjahn: University of Erlangen-Nuremberg
René E. M. Toes: Leiden University Medical Center
Martin Herrmann: University of Erlangen-Nuremberg
Hans Ulrich Scherer: Leiden University Medical Center
Georg Schett: University of Erlangen-Nuremberg

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7651

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