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Resetting the immune system to cure diabetes and rheumatism

In autoimmune diseases such as rheumatism and diabetes the immune system attacks autologous proteins. Leiden researchers are trying to discover how this comes about.

In autoimmune diseases such as rheumatism and diabetes the immune system attacks autologous proteins. Leiden researchers are trying to discover how this comes about. In the case of diabetes it is now clear which immune cells have become disturbed and what they are reacting against. This knowledge has made it possible to develop a new kind of cell therapy. The first clinical trials are due to start shortly. In the case of rheumatism the cause cannot be traced back to one type of immune cell, but ways are being sought to prevent the illness becoming chronic.

New cell therapy against diabetes

With diabetes the immune system destroys the insulin-producing beta cells in the pancreas. ‘To date treatment is only about managing the symptoms. We inject insulin, but we do nothing about the cause of the disease, namely the disrupted immune system,’ says Professor of Diabetology Bart Roep. He decided to find out exactly which cells go wrong in diabetes patients. T-cells, immune cells that normally protect the body against infections and cancer, seem to be the culprits. Roep discovered that these specific T-cells target a protein from the beta cells.

This information offered new possibilities. ‘We want to train the immune system not to respond to these proteins. To do that, we developed a kind of vaccine in the form of cell therapy.’ This vaccine is made up of immune cells from the patient in combination with the protein from the beta cells. Roep and his colleagues will shortly be starting the first clinical trials.

A human T-cell

Early treatment of rheumatism stops it becoming chronic

In the case of rheumatism, the immune system attacks the soft tissue of the joints, causing joint pain and inflammation. ‘An enormous amount of progress has been made in recent years in the treatment of rheumatism,’ explains rheumatologist Annette van der Helm. ‘Joint damage is now very rare, because we have better medicines, but also because we start treatment earlier, and take immediate action if and when the disease flares up.’ Nonetheless, it’s a disease that’s difficult to cure. Patients continue to suffer from joint pain, disability and fatigue. In many cases they have to take medicines all their lives.

Unfortunately, we do not know exactly what goes wrong in the immune system in the case of rheumatism, although specific autoantibodies (antibodies that attack the body’s own tissues) have been identified for this disease. ‘It isn’t that the immune system attacks a single specific antigen, which is why we don’t understand why it’s a chronic disease. What we do know is that the immune response that causes rheumatism is already present years before people become sick. We also know that this immune response becomes more widespread and matures around six months before the first symptoms are felt. We want to know what causes this maturation and how we can prevent it. We believe that if we can prevent this faulty immune response, we can stop people suffering from rheumatism. This is why we are starting treatment earlier and earlier. Ideally, we want to intervene before the immune system matures so that the disease doesn’t have the chance to become chronic,’ comments Van der Helm.

Study on early treatment

It sounds simpler than it is. ‘Patients often only come to us once the illness is visible externally in the form of swelling of the joints, but by then the illness is already chronic.’ With this in mind, Van der Helm carries out research among a large group of people who only suffer from joint pain. She uses MRI to see whether their joints are inflamed inside. If they are, these patients can then take part in a clinical trial aimed at studying whether very early treatment at this stage of the disease can prevent rheumatism from becoming chronic. This trial will generate unique data about the maturation of the autoantibody response and the link with remission. Van der Helm also wants to understand more about the mechanisms that contribute to the disease becoming chronic, but this calls for a lot more research.

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