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

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; Mattias Collin; Kim Kultima; Birgitta Heyman; Juan Miguel Jimenez-Andrade; Simone Codeluppi; Rikard Holmdahl; Camilla I Svensson

doi:10.1084/jem.20181657

Standard

Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons. / Bersellini Farinotti, Alex; Wigerblad, Gustaf; Nascimento, Diana; Bas, Duygu B; Morado Urbina, Carlos; Nandakumar, Kutty Selva; Sandor, Katalin; Xu, Bingze; Abdelmoaty, Sally; Hunt, Matthew A; Ängeby Möller, Kristina; Baharpoor, Azar; Sinclair, Jon; Jardemark, Kent; Lanner, Johanna T; Khmaladze, Ia; Borm, Lars E; Zhang, Lu; Wermeling, Fredrik; Cragg, Mark S; Lengqvist, Johan; Chabot-Doré, Anne-Julie; Diatchenko, Luda; Belfer, Inna; Collin, Mattias; Kultima, Kim; Heyman, Birgitta; Jimenez-Andrade, Juan Miguel; Codeluppi, Simone; Holmdahl, Rikard; Svensson, Camilla I.

I: Journal of Experimental Medicine, Vol. 216, Nr. 8, 2019, s. 1904-1924.

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift

Harvard

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 2019, 'Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons', Journal of Experimental Medicine, vol. 216, nr. 8, s. 1904-1924. https://doi.org/10.1084/jem.20181657

APA

Bersellini Farinotti, A., Wigerblad, G., Nascimento, D., Bas, D. B., Morado Urbina, C., Nandakumar, K. S., Sandor, K., Xu, B., Abdelmoaty, S., Hunt, M. A., Ängeby Möller, K., Baharpoor, A., Sinclair, J., Jardemark, K., Lanner, J. T., Khmaladze, I., Borm, L. E., Zhang, L., Wermeling, F., ... Svensson, C. I. (2019). Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons. Journal of Experimental Medicine, 216(8), 1904-1924. https://doi.org/10.1084/jem.20181657

CBE

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. 2019. Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons. Journal of Experimental Medicine. 216(8):1904-1924. https://doi.org/10.1084/jem.20181657

MLA

Bersellini Farinotti, Alex et al. "Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons". Journal of Experimental Medicine. 2019, 216(8). 1904-1924. https://doi.org/10.1084/jem.20181657

Vancouver

Bersellini Farinotti A, Wigerblad G, Nascimento D, Bas DB, Morado Urbina C, Nandakumar KS et al. Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons. Journal of Experimental Medicine. 2019;216(8):1904-1924. https://doi.org/10.1084/jem.20181657

Author

Bersellini Farinotti, Alex ; Wigerblad, Gustaf ; Nascimento, Diana ; Bas, Duygu B ; Morado Urbina, Carlos ; Nandakumar, Kutty Selva ; Sandor, Katalin ; Xu, Bingze ; Abdelmoaty, Sally ; Hunt, Matthew A ; Ängeby Möller, Kristina ; Baharpoor, Azar ; Sinclair, Jon ; Jardemark, Kent ; Lanner, Johanna T ; Khmaladze, Ia ; Borm, Lars E ; Zhang, Lu ; Wermeling, Fredrik ; Cragg, Mark S ; Lengqvist, Johan ; Chabot-Doré, Anne-Julie ; Diatchenko, Luda ; Belfer, Inna ; Collin, Mattias ; Kultima, Kim ; Heyman, Birgitta ; Jimenez-Andrade, Juan Miguel ; Codeluppi, Simone ; Holmdahl, Rikard ; Svensson, Camilla I. / Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons. I: Journal of Experimental Medicine. 2019 ; Vol. 216, Nr. 8. s. 1904-1924.

RIS

TY - JOUR

T1 - Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons

AU - Bersellini Farinotti, Alex

AU - Wigerblad, Gustaf

AU - Nascimento, Diana

AU - Bas, Duygu B

AU - Morado Urbina, Carlos

AU - Nandakumar, Kutty Selva

AU - Sandor, Katalin

AU - Xu, Bingze

AU - Abdelmoaty, Sally

AU - Hunt, Matthew A

AU - Ängeby Möller, Kristina

AU - Baharpoor, Azar

AU - Sinclair, Jon

AU - Jardemark, Kent

AU - Lanner, Johanna T

AU - Khmaladze, Ia

AU - Borm, Lars E

AU - Zhang, Lu

AU - Wermeling, Fredrik

AU - Cragg, Mark S

AU - Lengqvist, Johan

AU - Chabot-Doré, Anne-Julie

AU - Diatchenko, Luda

AU - Belfer, Inna

AU - Collin, Mattias

AU - Kultima, Kim

AU - Heyman, Birgitta

AU - Jimenez-Andrade, Juan Miguel

AU - Codeluppi, Simone

AU - Holmdahl, Rikard

AU - Svensson, Camilla I

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1084/jem.20181657

DO - 10.1084/jem.20181657

M3 - Article

C2 - 31196979

VL - 216

SP - 1904

EP - 1924

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 1540-9538

IS - 8

ER -