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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Alex Bersellini Farinotti
  • Gustaf Wigerblad
  • Diana Nascimento
  • Duygu B Bas
  • Carlos Morado Urbina
  • Kutty Selva Nandakumar
  • Katalin Sandor
  • Bingze Xu
  • Sally Abdelmoaty
  • Matthew A Hunt
  • Kristina Ängeby Möller
  • Azar Baharpoor
  • Jon Sinclair
  • Kent Jardemark
  • Johanna T Lanner
  • Ia Khmaladze
  • Lars E Borm
  • Lu Zhang
  • Fredrik Wermeling
  • Mark S Cragg
  • Johan Lengqvist
  • Anne-Julie Chabot-Doré
  • Luda Diatchenko
  • Inna Belfer
  • Kim Kultima
  • Birgitta Heyman
  • Juan Miguel Jimenez-Andrade
  • Simone Codeluppi
  • Rikard Holmdahl
  • Camilla I Svensson
Enheter & grupper
Externa organisationer
  • Karolinska Institute
  • Southern Medical University
  • Karolinska University Hospital
  • McGill University
  • Uppsala universitet
  • University of Southampton
  • National Institutes of Health, United States
  • Autonomous University Of Tamaulipas
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper
  • Immunologi inom det medicinska området
Originalspråkengelska
Sidor (från-till)1904-1924
TidskriftJournal of Experimental Medicine
Volym216
Utgåva nummer8
Tidigt onlinedatum2019 jun 13
StatusPublished - 2019
PublikationskategoriForskning
Peer review utfördJa

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