Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons.

Journal Article (Journal Article)

Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. smFISH and IHC suggest that neuronal Fcgr1 and Fcgr2b mRNA are transported to peripheral ends of primary afferents. CII-ICs directly activate cultured WT but not FcRγ chain-deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcRγ chain-deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcRγ chain-deficient mice or mice lacking activating FcγRs in neurons. In summary, this study defines functional coupling between autoantibodies and pain transmission that may facilitate the development of new disease-relevant pain therapeutics.

Full Text

Duke Authors

Cited Authors

  • Bersellini Farinotti, A; Wigerblad, G; Nascimento, D; Bas, DB; Morado Urbina, C; Nandakumar, KS; Sandor, K; Xu, B; Abdelmoaty, S; Hunt, MA; Ängeby Möller, K; Baharpoor, A; Sinclair, J; Jardemark, K; Lanner, JT; Khmaladze, I; Borm, LE; Zhang, L; Wermeling, F; Cragg, MS; Lengqvist, J; Chabot-Doré, A-J; Diatchenko, L; Belfer, I; Collin, M; Kultima, K; Heyman, B; Jimenez-Andrade, JM; Codeluppi, S; Holmdahl, R; Svensson, CI

Published Date

  • August 5, 2019

Published In

Volume / Issue

  • 216 / 8

Start / End Page

  • 1904 - 1924

PubMed ID

  • 31196979

Pubmed Central ID

  • PMC6683987

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20181657


  • eng

Conference Location

  • United States