He seeks new ways to treat rheumatoid arthritis

Rheumatoid arthritis, also known as RA, is an autoimmune disease in which the body’s immune system mistakenly begins to attack its own tissues. The symptoms often start in the small joints of the hands and feet and can then spread throughout the body.

The disease was previously associated with significant suffering and could lead to severe disability and inflammation in internal organs, sometimes with fatal outcomes. Today, most people have a good prognosis and can live a normal life, even though rheumatoid arthritis cannot be cured.

There is, however, still a group of patients who do not benefit fully from today’s treatments. Some continue to experience symptoms such as pain, swelling and severe fatigue. The size of this group differs between countries, depending on which treatments are available.

“Up to 20 per cent of patients are estimated to have a form of the disease that is difficult to treat. Why some respond poorly to treatment is still not fully understood,” says Mattias Svensson, a researcher at the Department of Rheumatology and Inflammation Research at the University of Gothenburg.

Develops cancer-like behaviour

One of the key drivers in the development of rheumatoid arthritis is the so‑called synovial fibroblast. These cells are a type of connective tissue cell that lines a thin membrane on the inside of the joint. 

They normally play an important role by producing nutrients and keeping the joint fluid clean. In rheumatoid arthritis, however, they develop cancer‑like behaviour, increasing in number, driving inflammation and contributing to the destruction of cartilage within the joint.

Together with his colleagues, Mattias Svensson is investigating how synovial fibroblasts interact with the immune system — both to understand how this behaviour begins and to explore how it might be stopped.

“We believe that the immune system senses some form of damage and signals the synovial fibroblasts to repair it. Because the inflammation becomes chronic, the signal simply continues, which may cause the fibroblasts to adapt and develop this destructive behaviour,” he says.

In earlier studies, Mattias Svensson and his colleagues discovered that people with rheumatoid arthritis have elevated levels of a protein called amphiregulin. The protein is released by certain immune cells, including innate lymphoid cells (ILCs). Under normal circumstances, amphiregulin helps regulate cell growth and supports tissue repair.

“Our hypothesis is that these immune cells, the ILCs, accumulate in the joint and release amphiregulin. Over time, this leads the synovial fibroblasts to develop this destructive behaviour,” he says.

Investigates the interplay with nerve cells

There are currently no drugs that directly target the disease mechanisms in the arthritic joint. Today’s medications act more broadly, for example by reducing inflammation throughout the body.

The goal of Mattias Svensson’s research is to understand the disease mechanisms in greater detail, so that more effective drugs can be developed that directly target the disease process itself.

Two possible approaches are to inhibit the immune cells’ production of amphiregulin, or to block the signal that the immune cells send to the synovial fibroblasts.

“There is extensive research underway, and several drugs have already been tested. Unfortunately, the results have not been sufficient. One of the main challenges is that fibroblasts are present throughout the body, not only in the joints. The goal is therefore to find a treatment that acts locally without negatively affecting the immune system. Our animal studies indicate that it is possible to eliminate amphiregulin without causing any major adverse effects,” he says.

Mattias Svensson is also exploring how pain itself may influence inflammatory processes, and how interactions between neuronal and immune cells can contribute to disease progression. In some patients, pain may persist even when the underlying inflammation is well controlled.

“Perhaps the nerve cells continue to activate immune cells, thereby driving a vicious cycle that we need to find a way to break. How the nervous and immune systems interact to regulate inflammation is highly intriguing, and remains a relatively unexplored area in rheumatoid arthritis,” he says. 

More common in women

Rheumatoid arthritis is three times more common in women than in men. This is thought to be due in part to sex hormones, but sex chromosomes may also contribute. This latter aspect is something Mattias Svensson is also exploring, in collaboration with researchers at Lund University and Uppsala University.

“At a group level, men are generally more susceptible to infections, while women are more prone to autoimmune diseases. The X chromosomes contain many components that are important for the immune system, and women have two of them. We have found an exciting way to study this, although I prefer not to go into details at this point. But we have conducted an interesting study that I hope will be published later this year,” he says.

It is not yet clear where autoimmune diseases begin, or why. These conditions can develop slowly over many years. Some patients can show detectable antibodies up to 20 years before the disease manifests.

One theory is that the disease originates in the lungs. Smoking significantly increases the risk of rheumatoid arthritis. The other theory is that it begins in the gut. This is something Mattias Svensson investigated during his postdoctoral research at the La Jolla Institute for Immunology in San Diego, USA.

“There is a gene that increases the risk of both inflammatory bowel disease and rheumatoid arthritis. We were able to show that mice carrying this gene developed rheumatoid arthritis both when they were given a low‑grade inflammation in the gut and when they received gut bacteria from patients with rheumatoid arthritis,” he says.

Passion for discovery

Mattias Svensson grew up in Skåne. After finishing high school, he considered becoming either an architect or a nurse but eventually chose the biomedical field. He was curious about research, an interest that deepened when he completed his master’s thesis in Canada. Back in Sweden, he began his PhD studies at the Sahlgrenska Academy. He defended his thesis in 2014 and then spent nearly six years in the United States.

“It was an incredibly inspiring and enjoyable period, both professionally and personally, living in California. There were enormous resources and an exceptional drive. It felt as though almost anything was possible. At our seminars, Nobel laureates and leading immunologists would come and lecture. At the same time, you had to work extremely hard. There wasn’t exactly a work–life balance,” he says.

In early 2020, he returned to the University of Gothenburg to establish his own research group. Since 2024, he has also served as head of division. Practical lab work is still what he enjoys the most, even though administrative duties now take up a larger share of his time — from applying for grants to leading the division forward and creating an inspiring environment where his colleagues can thrive.

“I think what drives me most is the joy of discovering new things. For me, the best moments are still the ones spent in the lab, watching what unfolds in different experiments. To build and test a hypothesis is still incredibly exciting. Even though we know a great deal, there is still an incredible amount left to discover,” he says.

TEXT AND PHOTOS: KARIN ALLANDER