Scientists identify a cause of lupus and open the door to new medical treatments

NBC News

A key mystery behind one of the most common autoimmune diseases may finally have an answer.

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

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

Now, a study published Wednesday in the journal Nature outlines a clear pathway for the likely development of the disease, 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 lupus patients produce,” said Dr. Deepak Rao, one of the study’s authors and a rheumatologist at Brigham and Women’s Hospital in Massachusetts. T cells are white blood cells that play a key role in the body’s immune response.

The study reached its conclusions by comparing blood samples from 19 people with lupus with those from healthy individuals. The comparison showed that people with lupus have too much of a particular T cell associated with damage to 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 the body defend itself against pathogens. Scientists have known for many years that people with lupus have excessive amounts of type I interferon, but the new study links this problem to several 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 hampers the production of T cells that can help heal wounds in the skin, lung and gut barrier. It also stimulates the production of T cells involved in creating autoantibodies, which attack healthy cells and are a hallmark of lupus.

According to Rao, this theory could explain the vast majority of lupus cases.

“I think this will apply to essentially all lupus patients,” she said.

But other experts questioned the idea that there is a single explanation for all lupus cases.

“This is very interesting and encouraging research, but I think it may be too early to say that this is the primary cause of the disease,” said Mara Lennard Richard, scientific program officer for the Lupus Research Alliance. The Alliance is a private funder of lupus research and supported Rao’s study with a grant.

Because lupus symptoms are so varied and the contributing factors are so many, “it’s been very difficult to find a root cause of the disease,” Lennard Richard said. “Obviously, if this turns out to be the cause of lupus, that would be amazing and really fantastic for people living with it.”

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

“Until they study 100 patients prospectively, how are we going to know?” said Buyon, who was not involved in the study.

The Centers for Disease Control and Prevention (CDC) estimates that more than 200,000 people in the United States have lupus, although the Lupus Foundation of America says the number is much higher: approximately 1.5 million people. About 90% of people with lupus are women.

The most common symptoms are extreme fatigue, joint pain or skin rashes. In rare cases, the disease can damage the kidneys or heart, or weaken the immune system so that the body cannot fight off infections. These problems can be fatal or life-threatening.

Historically, lupus has been difficult to treat. Many of the current options widely suppress the immune system, including beneficial T cells that fight infections. And for some people with the disease, standard treatments are not effective.

According to Dr. Jaehyuk Choi, one of the study’s authors and a dermatologist at Northwestern Medicine, the new research points to the possibility of better treatments in the future, which could be infusions or tablets.

The study found that giving people with lupus anifrolumab, a drug that blocks interferon, prevented the T-cell imbalance that likely causes the disease.

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

In blood samples from 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 buildup of disease-promoting T cells.

According to Choi, the main challenge in developing a new treatment is finding a way to administer it without activating arylhydrocarbon receptors throughout the body, which could lead to more side effects.

Buyon said that even if such a treatment were to become available, it is unlikely to work for all lupus patients.

“We have come to the deep conviction that one drug does not work for everything,” he said.