Effects of Autoantibodies on Osteoclasts

Abstract

The balance between bone forming osteoblasts and bone resorbing osteoclasts can be disturbed in autoimmune diseases resulting in local and systemic bone loss. It was long time believed that autoantibodies only indirectly contribute to bone loss by fueling the overall inflammation. However, in the last decade, more and more evidence emerged that autoantibodies and immune complexes directly activate osteoclasts and pre-osteoclasts by binding to Fcγ receptors (FcγRs) on the (pre)-osteoclast cell surface. This pro-osteoclastogenic effect seems to be dependent on the absence of sialic acid in the IgG Fc glycan, which is a typical feature of many autoantibodies. Clinical studies revealed the importance of autoantibody-mediated bone loss mainly in rheumatoid arthritis, but also in other diseases, such as celiac disease. In summary, the gained knowledge about autoantibody-mediated bone loss helps to better understand bone pathologies of autoimmune diseases. However, studies are still relatively limited and more research is needed to fully understand the impact of autoantibodies on bone and to develop future therapeutic strategies.

Zusammenfassung

Das Gleichgewicht zwischen knochenbildenden Osteoblasten und knochenresorbierenden Osteoklasten kann bei Autoimmunerkrankungen gestört sein, wodurch es zu lokalem und systemischem Knochenverlust kommt. Es wurde lange Zeit angenommen, dass Autoantikörper nur indirekt zum Knochenverlust beitragen, indem sie die Entzündung befeuern. In den letzten zehn Jahren gab es jedoch immer mehr Hinweise darauf, dass Autoantikörper und Immunkomplexe Osteoklasten und Präosteoklasten direkt aktivieren, indem sie an Fcγ-Rezeptoren (FcγRs) auf der (Prä-) Osteoklastenoberfläche binden. Diese pro-osteoklastogene Wirkung scheint von der Abwesenheit von Sialinsäure im IgG-Fc-Glykan abhängig zu sein, was ein typisches Merkmal vieler Autoantikörper ist. Klinische Studien zeigten die Bedeutung des autoantikörpervermittelten Knochenverlusts hauptsächlich bei rheumatoider Arthritis, aber auch bei anderen Krankheiten wie Zöliakie. Zusammengenommen hilft das gewonnene Wissen über autoantikörpervermittelten Knochenverlust, die Knochenpathologien von Autoimmunerkrankungen besser zu verstehen. Bisher gibt es jedoch nur relativ wenige Studien und es sind weitere Forschungsarbeiten erforderlich, um die Auswirkungen von Autoantikörpern auf den Knochen vollständig zu verstehen und zukünftige Therapiestrategien zu entwickeln.

Key words

bone loss - osteoclast - autoantibodies - autoimmunity - glycosylation

Schlüsselwörter

Knochenverlust - Osteoklast - Autoantikörper - Autoimmunität - Glykosylierung

Publication History

Received: 21 May 2021

Accepted: 11 August 2021

Article published online:
23 September 2021

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