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

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title = "Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons",
abstract = "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.",
author = "{Bersellini Farinotti}, Alex and Gustaf Wigerblad and Diana Nascimento and Bas, {Duygu B} and {Morado Urbina}, Carlos and Nandakumar, {Kutty Selva} and Katalin Sandor and Bingze Xu and Sally Abdelmoaty and Hunt, {Matthew A} and {{\"A}ngeby M{\"o}ller}, Kristina and Azar Baharpoor and Jon Sinclair and Kent Jardemark and Lanner, {Johanna T} and Ia Khmaladze and Borm, {Lars E} and Lu Zhang and Fredrik Wermeling and Cragg, {Mark S} and Johan Lengqvist and Anne-Julie Chabot-Dor{\'e} and Luda Diatchenko and Inna Belfer and Mattias Collin and Kim Kultima and Birgitta Heyman and Jimenez-Andrade, {Juan Miguel} and Simone Codeluppi and Rikard Holmdahl and Svensson, {Camilla I}",
note = "{\textcopyright} 2019 Bersellini Farinotti et al.",
year = "2019",
doi = "10.1084/jem.20181657",
language = "English",
volume = "216",
pages = "1904--1924",
journal = "Journal of Experimental Medicine",
issn = "1540-9538",
publisher = "Rockefeller University Press",
number = "8",