He discovered the mechanisms behind SLE at an early stage

SLE is an autoimmune disease that affects around 7,000 people in Sweden – many of them women. In Latin, the disease is called “systemic lupus erythematosus”. It also goes by the name “red wolf disease”, so named because the rash was originally thought to look like a wolf’s bite.

Researchers at Uppsala University were among the first to conduct research on the disease, led by Lars Rönnblom, Professor of Rheumatology.

It all started with the discovery of a side effect in cancer patients treated with interferon at Uppsala University Hospital in the 1980s.

“Interferon is a protein produced by virus-infected cells that has antiviral effects. In other words, it protects other cells from becoming infected. Interferon is what causes us to develop a fever and muscle pain, and to feel tired when we are ill with the flu or the like,” explains Lars Rönnblom.

Treatment for cancer patients

The Uppsala Biomedical Centre (BMC) began producing interferon as early as the late 1970s. After discovering that interferon not only protects against viruses but also stimulates the immune system, Uppsala University Hospital began using interferon in its treatment of cancer patients.

Back then, Lars Rönnblom was a PhD student tasked with finding out which cells produced interferon. He presented the results in his doctoral thesis.

“It was a very special type of cell that I called natural interferon-producing cells. They were extremely rare, one in a thousand among the circulating white blood cells, and one such cell could produce a hundred million proteins in 24 hours. So, it was a formidable factory.”

Met patients with SLE

After earning his PhD, Lars Rönnblom began working clinically. As a doctor, he came into contact with cancer patients who had been treated with interferon, and several of them had developed autoimmune or rheumatic diseases.

Among the more dramatic patient cases was a young woman with metastatic abdominal cancer. After treatment, the tumour disappeared, but she was left with SLE.

“When I saw that, I decided that I just had to learn how some of the regular patients at the rheumatology clinic had spontaneously developed SLE,” says Lars Rönnblom.

At that time, in 1995 to be exact, he had started working as a rheumatologist at Uppsala University Hospital.

It emerged that patients with SLE had strongly activated interferon in the body’s cells – and, what’s more, these were the same cells that Lars Rönnblom had described in his thesis.

Stimulated production

Through experiments, the researchers were able to show that SLE patients had molecules in their bodies that stimulated the production of interferon. The cells migrated into the tissues and produced large amounts of interferon, which drove the disease process.

“We were able to show which molecules were involved and how it worked. But it was almost impossible to get the research results published, because no one really believed it,” says Lars Rönnblom.

This was the case until 2003, when four so-called gene expression studies were published that showed increased expression of interferon-related genes in patients with SLE.

“Suddenly, our studies were in demand. I was invited to the United States and received substantial funding to continue researching the genetics behind SLE.”

The researchers went on to investigate what happens when these genes are blocked, in order to develop effective antibodies that can be used to treat SLE. The first preparation, a prescription drug which can be administered by injection, was recently registered.

Risk of severe disease

They are also researching how to identify patients who are at risk of developing severe disease.

“Some patients develop and suffer from skin rashes. But we doctors do not consider this life-threatening, like when organs such as the kidneys and heart are affected,” says Lars Rönnblom.

SLE is considered the prototype for autoimmune diseases, partly because there are so many antibodies and partly because all organs can be attacked. The disease often affects women of childbearing age.

“It can start with internal organ manifestations; it can start with psychological symptoms, miscarriage or heart disease, so it's an insidious disease.”

More new drugs needed

Until now, SLE has been treated with cortisone and immunosuppressive drugs, which have the disadvantage of causing serious long-term side effects. Malaria drugs have also been shown to have some effect. However, it has been difficult to develop new drugs because the disease is so heterogeneous.

“Many new biological drugs have been developed, but so far only two biological drugs for SLE. So, simply put, more are needed – and they will come,” says Lars Rönnblom.

Annica Hulth