期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 216, 期 8, 页码 1904-1924出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20181657
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资金
- Swedish Research Council
- Swedish Foundation for Strategic Research
- Knut och Alice Wallenberg Foundation
- Ragnar Soderberg Foundation
- Torsten Soderberg Foundation
- Ake Wiberg Foundation
- Alfred Osterlund Foundation
- Konung Gustaf V's 80-year foundation
- Swedish Arthritis Association
- Hansa Medical AB
- Royal Physiographic Society in Lund
- Karolinska Institutet
- Canadian Institutes of Health Research [G237818/CERC09/CIHR]
- Government of Guangdong Province [201001Y04675344]
- GyllenstiernaKrapperup Foundation
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 FcR gamma chain-deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcR gamma chain-deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcR gamma chain-deficient mice or mice lacking activating Fc gamma Rs 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.
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