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Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.ORCID iD: 0000-0003-3765-4801
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
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2019 (English)In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 216, no 8, p. 1904-1924Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
ROCKEFELLER UNIV PRESS , 2019. Vol. 216, no 8, p. 1904-1924
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Immunology in the medical area
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URN: urn:nbn:se:uu:diva-394167DOI: 10.1084/jem.20181657ISI: 000482810500016PubMedID: 31196979OAI: oai:DiVA.org:uu-394167DiVA, id: diva2:1359361
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Swedish Research CouncilSwedish Foundation for Strategic Research Knut and Alice Wallenberg FoundationAvailable from: 2019-10-09 Created: 2019-10-09 Last updated: 2019-10-09Bibliographically approved

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