Scholarship for the treatment of rheumatism

Rheumatoid arthritis is chronic inflammation of the joints

Prevent rheumatism? According to the LUMC researchers, this is by no means a daydream: they are now receiving a € 10 million Synergy Grant from the European Research Council to deepen their strategy. It is the first time that a UMC in the Netherlands leads such a project. Researchers are building on their discovery that rheumatism patients have glycated antibodies in their blood in the years before they develop symptoms. “If the factories that produce these antibodies are inhibited, we expect rheumatism to be prevented,” says rheumatology professor Tom Huizinga.

Rheumatoid arthritis is chronic inflammation of the joints. It is an autoimmune disease, which means that the immune system, immune cells, and antibodies turn against the body. “We have previously found that the antibodies that play a role in rheumatism are greater,” says Huizinga. “This is due to a sugar group that is blocked on the antibody. We have also seen that people who produce these saccharified antibodies later develop rheumatism ”. A crucial feature of the development of rheumatism.

Derailed cells
Not only these antibodies, but also the factories that produce these substances, the B lymphocytes, are affected by this extra sugar group. “We see that after a sugar group binds, the B lymphocytes become more active and derail a bit,” says experimental rheumatology professor René Toes. With this grant, the researchers want to find out how the sugar group binds to B lymphocytes and thus how these cells get angry. “If we know, we can block the binding of the sugar group with the B cell, and thus treat rheumatism in a targeted way, or even prevent it.”

It may sound simple, but it requires a lot of experience. And not just about the disease itself and the underlying immunology, but also about the function and structure of sugar groups. That is why Professor of Proteomics and Glycomics, Manfred Wuhrer, is closely involved. Using advanced techniques to identify the molecules, he found that rheumatoid antibodies are larger. “The connection between clinic, laboratory and technology forms the basis of this project. It is the strength behind our previous successes and it is unique that these skills can be found under one roof, ”says Wuhrer.

postpone rheumatism
LUMC researchers, who had previously conducted a study with support from ReumaNederland, wrote in The Lancet this year that rheumatism can be postponed if patients are treated before they develop rheumatism. “This gives us hope,” says Huizinga. “It provides evidence that we can catch rheumatism patients before they develop rheumatism, and this is exactly the group we want to treat,” says Huizinga. “So there is already a clinical infrastructure in place to test our strategy on patients.”

Popular objects
About 270,000 people in the Netherlands suffer from rheumatoid arthritis. The first symptoms often begin around the age of 50 and are very disabling. Due to pain and stiffness in the joints, people are often unable to work. “We are getting better at treating rheumatism, for example with drugs targeting inflammatory hormones,” says Toes. “It works well, but it is expensive. If we can prevent rheumatism, we not only save a lot of suffering, but also a lot of money ”.

Researchers continually point out that this is by no means a daydream. “We have been working on it for about 20 years and we really think it could work. It’s great that ERC sees this too. We expect to go a long way with this large grant, “says Huizinga.” To ultimately create targeted therapy for this common disease, “concludes Toes.

RheumaNederland
Corné Baatenburg de Jong, Deputy Director of ReumaNederland: “It is great that our funding options have brought the research here and that it was possible to apply for an ERC. To the next step. Early diagnosis and early treatment are one of our important topics. People with early (rheumatic) disorders should be given an adequate diagnosis and the right treatment as soon as possible. So that they know where they are and that unnecessary harm to health can be prevented. Or better still: so that the disease does not develop and can even be prevented ».

ERC synergy
ERC Synergy grants are aimed at bold scientific challenges and only innovative research proposals are eligible. The project team, led by LUMC, is made up of four researchers, including Huizinga and Wuhrer, who will each receive € 2.5 million. The Leiden researchers are working together with Salome Pinho from Portugal and Gordan Lauc from Croatia.