Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin

Ulrike Harre, Dan Georgess, Holger Bang, Aline Bozec, Roland Axmann, Elena Ossipova, Per Johan Jakobsson, Wolfgang Baum, Falk Nimmerjahn, Eszter Szarka, G. Sármay, Grit Krumbholz, Elena Neumann, Rene Toes, Hans Ulrich Scherer, Anca Irinel Catrina, Lars Klareskog, Pierre Jurdic, Georg Schett

Research output: Contribution to journalArticle

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Abstract

Autoimmunity is complicated by bone loss. In human rheumatoid arthritis (RA), the most severe inflammatory joint disease, autoantibodies against citrullinated proteins are among the strongest risk factors for bone destruction. We therefore hypothesized that these autoantibodies directly influence bone metabolism. Here, we found a strong and specific association between autoantibodies against citrullinated proteins and serum markers for osteoclast-mediated bone resorption in RA patients. Moreover, human osteoclasts expressed enzymes eliciting protein citrullination, and specific N-terminal citrullination of vimentin was induced during osteoclast differentiation. Affinity-purified human autoantibodies against mutated citrullinated vimentin (MCV) not only bound to osteoclast surfaces, but also led to robust induction of osteoclastogenesis and boneresorptive activity. Adoptive transfer of purified human MCV autoantibodies into mice induced osteopenia and increased osteoclastogenesis. This effect was based on the inducible release of TNF-α from osteoclast precursors and the subsequent increase of osteoclast precursor cell numbers with enhanced expression of activation and growth factor receptors. Our data thus suggest that autoantibody formation in response to citrullinated vimentin directly induces bone loss, providing a link between the adaptive immune system and bone.

Original languageEnglish
Pages (from-to)1791-1802
Number of pages12
JournalJournal of Clinical Investigation
Volume122
Issue number5
DOIs
Publication statusPublished - May 1 2012

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Vimentin
Osteoclasts
Osteogenesis
Autoantibodies
Bone and Bones
Rheumatoid Arthritis
Proteins
Growth Factor Receptors
Adoptive Transfer
Joint Diseases
Metabolic Bone Diseases
Bone Resorption
Autoimmunity
Immune System
Cell Count
Biomarkers
Enzymes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Harre, U., Georgess, D., Bang, H., Bozec, A., Axmann, R., Ossipova, E., ... Schett, G. (2012). Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. Journal of Clinical Investigation, 122(5), 1791-1802. https://doi.org/10.1172/JCI60975

Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. / Harre, Ulrike; Georgess, Dan; Bang, Holger; Bozec, Aline; Axmann, Roland; Ossipova, Elena; Jakobsson, Per Johan; Baum, Wolfgang; Nimmerjahn, Falk; Szarka, Eszter; Sármay, G.; Krumbholz, Grit; Neumann, Elena; Toes, Rene; Scherer, Hans Ulrich; Catrina, Anca Irinel; Klareskog, Lars; Jurdic, Pierre; Schett, Georg.

In: Journal of Clinical Investigation, Vol. 122, No. 5, 01.05.2012, p. 1791-1802.

Research output: Contribution to journalArticle

Harre, U, Georgess, D, Bang, H, Bozec, A, Axmann, R, Ossipova, E, Jakobsson, PJ, Baum, W, Nimmerjahn, F, Szarka, E, Sármay, G, Krumbholz, G, Neumann, E, Toes, R, Scherer, HU, Catrina, AI, Klareskog, L, Jurdic, P & Schett, G 2012, 'Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin', Journal of Clinical Investigation, vol. 122, no. 5, pp. 1791-1802. https://doi.org/10.1172/JCI60975
Harre, Ulrike ; Georgess, Dan ; Bang, Holger ; Bozec, Aline ; Axmann, Roland ; Ossipova, Elena ; Jakobsson, Per Johan ; Baum, Wolfgang ; Nimmerjahn, Falk ; Szarka, Eszter ; Sármay, G. ; Krumbholz, Grit ; Neumann, Elena ; Toes, Rene ; Scherer, Hans Ulrich ; Catrina, Anca Irinel ; Klareskog, Lars ; Jurdic, Pierre ; Schett, Georg. / Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. In: Journal of Clinical Investigation. 2012 ; Vol. 122, No. 5. pp. 1791-1802.
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