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BREAKING NEWS
Source: Thailand Medical News  Jul 15, 2019
New Discovery That Antibodies Are The Cause Of Rheumatoid Arthritic Pain
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New Discovery That Antibodies Are The Cause Of Rheumatoid Arthritic Pain
Source: Thailand Medical News  Jul 15, 2019
Rheumatoid arthritis is an autoimmune disease that occurs when immune cells attack the cartilage and bone of the joints. The disease affects roughly 1.4 percent of the global population. A common symptom is joint pain, but even before that, the body has started to produce immune antibodies against proteins in the joint. Scientists at Karolinska Institute in Sweden, have now discovered  how these autoantibodies can generate pain. The results from this study can facilitate the development of new ways of reducing non-inflammatory pain caused by rheumatoid arthritis and other autoimmune diseases.



The researchers injected cartilage-binding autoantibodies into animal models, which served as a model for human rheumatoid arthritis, and subsequently discovered that the animal models became more sensitive to pain even before they could observe any signs of inflammation in the joints. Antibodies that had been designed not to activate immune cells and trigger inflammation also induced pain-like behaviour in the animal models, suggesting increased pain sensitivity in the joints.

The team found that the antibodies that caused the behavioural 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.When they cultivated pain neurons from the animal models, the team found that the cells were activated when coming into contact with the antibody complexes. The process was dependent upon the Fc-gamma receptors on the neurons but not on the presence of immune cells. Antibodies in complex can thus act as pain-generating molecules in themselves, independently of the activity of the immune cells.

Antibodies in these immune complexes can activate the pain neurons directly, and not, as previously thought, as a result of the destructive joint inflammation. The antibodies can affect the pain neurons also in conditions without any distinct tissue damage or inflammation.Though the study was conducted in animal models, the team show that human pain neurons also have antibody receptors that are functionally similar to those they found on the animal model pain neurons, which leads them to believe that their findings are also relevant to humans.

These findings help 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 ie the  autoantibody, the team believe that it can explain non-inflammatory pain caused by other autoimmune diseases too. Further detailed study of what happens in the nerve cell when the antibody complex binds to the receptor could also lead to new targets for reducing the neuronal activity.

One of the researchers holds a patent on the use of a type of antibody used in the study and a royalty agreement with Hansa Medical, which also holds a patent on a particular application of the antibodies.

Reference: 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