Scientists say they have identified the root cause of lupus – one that could pave the way for new treatments

There may finally be an answer to a key mystery behind one of the most common autoimmune diseases.

Researchers at Northwestern Medicine and Brigham and Women’s Hospital say they have discovered the root cause of lupus, a disease that affects hundreds of thousands of people in the US.

Scientists have long suspected that a person’s genetics or hormones may predispose them to lupus, and that environmental factors such as a previous viral infection or exposure to certain chemicals may trigger the disease.

Now, a study published Wednesday in the journal Nature outlines a clear path for how the disease is likely to develop, pointing to abnormalities in the immune systems of people with lupus.

“What we found was this fundamental imbalance in the types of T cells that patients with lupus make,” said Dr. Deepak Rao, one of the study authors and a rheumatologist at Brigham and Women’s Hospital in Massachusetts. T-cells are white blood cells that play a central role in the body’s immune response.

The study reached its findings by comparing blood samples from 19 people with lupus to blood samples from healthy people. The comparison showed that people with lupus have too much of a particular T cell associated with damage in healthy cells and too little of another T cell associated with repair.

At the heart of this imbalance is a protein called interferon, which helps protect the body against pathogens. Scientists have known for years that people with lupus have excessive amounts of type I interferon – but the new study links this issue to some negative effects.

First, too much type I interferon can block a protein called the aryl hydrocarbon receptor, which helps regulate the body’s response to bacteria or environmental pollutants.

Blocking this receptor inhibits the production of T cells that can help heal wounds on the skin, lung and gut barriers. It also stimulates the production of T cells involved in creating auto-antibodies, which attack healthy cells and are a hallmark of lupus.

Rao said the theory could explain the vast majority of lupus cases.

“I think this will basically apply to all patients with lupus,” he said.

But other experts have questioned the idea that there is a singular explanation for every case of lupus.

“It’s very exciting research and very promising, but I think it might be too early to say that it’s the root cause of the disease,” said Mara Lennard Richard, science program officer for the Lupus Research Alliance. The alliance is a private funder of lupus research and provided grant funding for Rao’s study.

Because the symptoms of lupus are so varied and caused by so many factors, “it’s been very difficult to find a single root cause of the disease,” Lennard Richard said. “Obviously, if this was the cause of lupus, that would be great and great for people with lupus.”

Dr. Jill Buyon, director of the division of rheumatology and the Lupus Center at NYU Langone Health, said the theory needs to be tested in a larger sample of people.

“Until they do a prospective study of 100 patients, how will we know?” said Buyon, who was not involved in the study.

The Centers for Disease Control and Prevention estimates that more than 200,000 people in the US have lupus, although the Lupus Foundation of America puts the total much higher: about 1.5 million people. About 90% of people with lupus are women.

Common symptoms include extreme fatigue, joint pain or skin rash. In rare cases, the disease can lead to kidney or heart damage, or it can weaken the immune system so that the body is unable to fight infections. These issues can be fatal or life threatening.

Lupus has historically been difficult to treat. Many of the current options largely suppress the immune system, including beneficial T cells that fight infection. And for some people with the disease, standard treatments aren’t effective.

The new study suggests that there may be better treatments in the future, which could be in the form of infusions or pills, said Dr. Jaehyuk Choi, one of the study authors and a dermatologist at Northwestern Medicine.

The study found that people with lupus anifrolumab, a drug that blocks interferon, prevented the T-cell imbalance that can lead to the disease.

“We followed patients who received this as part of their clinical care and showed that this cell imbalance was fixed in patients who received the drug or was on the way to being fixed,” Choi said.

In blood samples of people with lupus, the researchers also tested the effects of adding a small molecule that activates the aryl hydrocarbon receptor. They found that it limited the accumulation of disease-promoting T cells.

The big challenge in developing a new treatment, according to Choi, is finding ways to administer it without activating aryl hydrocarbon receptors throughout the body, which can have more side effects such as it results.

Even if such a treatment becomes available, Buyon said, it’s unlikely to work for everyone with lupus.

“We have a deep understanding that one drug is not going to do it all,” she said.

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