Rheumatoid Arthritic Pain Could Be Caused by Antibodies

Antibodies that exist in the joints before the onset of rheumatoid arthritis can cause pain even in the absence of arthritis, report researchers from Karolinska Institutet in Sweden report. 

“Pain can appear before any sign of inflammation in the joints and can remain a problem after it has healed. Our aim was to find possible mechanisms to explain that, ” says Camilla Svensson, professor at the Department of Physiology and Pharmacology, Karolinska Institutet.

Rheumatoid arthritis is an autoimmune disease that occurs when immune cells attack the cartilage and bone of the joints. A common early symptom is joint pain, but even before that, the body has started to produce immune antibodies against proteins in the joint. Researchers at Karolinska Institutet have now studied how these autoantibodies can generate pain.

After injecting cartilage-binding autoantibodies into mice, the researchers found that the mice became more sensitive to pain even before they could observe any signs of inflammation in the joints. 

The researchers found that the antibodies that caused the behavioral change form so called immune complexes, comprising clusters of antibodies and cartilage proteins in the joints. These complexes activate pain cells via so-called Fc-gamma receptors, which the researchers discovered were present on pain neurons in the tissue.

“Antibodies in these immune complexes can activate the pain neurons directly, and not, as previously thought, as a result of the destructive joint inflammation,” she says. “The antibodies can affect the pain neurons also in conditions without any distinct tissue damage or inflammation.”

The results can explain the early pain symptoms in rheumatoid arthritis patients. However, joint and muscle pain are also common symptoms of other autoimmune diseases, and since this newly discovered mechanism operates through the constant part of the autoantibody, the researchers believe that it can explain non-inflammatory pain caused by other autoimmune diseases too.

“We think that this can be a general pain mechanism in effectively all autoimmune diseases in which these kinds of immune complexes form locally in tissue,” says Professor Svensson.

“By learning more about the molecular mechanisms of antibody-mediated pain we hope to lay the groundwork for a new way of reducing pain caused by rheumatoid arthritis and other autoimmune diseases,” says Rikard Holmdahl, the study’s other corresponding author.


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 M. Jimenez-Andrade, Simone Codeluppi, Rikard Holmdahl, Camilla I Svensson. Cartilage binding antibodies induce pain through immune complex mediated activation of neurons. Journal of Experimental Medicine, June 13, 2019; DOI: 10.1084/jem.20181657

Karolinska Institutet. “Rheumatoid arthritic pain could be caused by antibodies.” ScienceDaily. ScienceDaily, 13 June 2019. <www.sciencedaily.com/releases/2019/06/190613104531.htm>.

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