Scientists say they have identified a root cause of lupus — one that could pave the way for new treatments
An imbalance of T cells, which play a key role in the body’s immune response, could explain most cases of the disease, according to new research.
By Aria Bendix
A key mystery behind one of the most common autoimmune diseases may finally have an answer.
Researchers at Northwestern Medicine and Brigham and Women’s Hospital say they’ve discovered a root cause of lupus, a disease that affects hundreds of thousands of people in the U.S.
Scientists have long suspected that a person’s genetics or hormones may predispose them to lupus, and that the disease may be triggered by environmental factors like a previous viral infection or exposure to certain chemicals.
Now, a study published Wednesday in the journal Nature outlines a clear pathway for how the disease likely develops, 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 key role in the body’s immune response.
The study arrived at its findings by comparing blood samples from 19 people with lupus to blood samples from healthy individuals. 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 defend the body against pathogens. Scientists have known for many years that people with lupus have excess amounts of type I interferon — but the new study links this issue 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 hinders the production of T cells that can help heal wounds on the barrier of the skin, lungs and gut. It also stimulates the production of T cells involved in creating autoantibodies, 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 is going to apply to essentially all patients with lupus,” he said.
But other experts questioned the idea that there’s a singular explanation for all instances of lupus.
“It’s very exciting research and very hopeful, but I think that it might be too early to say that it’s the root 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 contributed grant funding to Rao’s study.
Because lupus symptoms are so varied and the contributing factors are manifold, “it’s been very hard to find one singular root cause for 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 lupus.”
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 estimates that more than 200,000 people in the U.S. have lupus, though the Lupus Foundation of America puts the total much higher: roughly 1.5 million people. Around 90% of people with lupus are women.
Common symptoms include extreme fatigue, joint pain or skin rashes. In rare cases, the disease may lead to kidney or heart damage, or weaken the immune system so the body can’t fight off infections. These issues can be fatal or life-threatening.
Lupus has historically been difficult to treat. Many of the current options broadly 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 hints at the possibility of better treatments in the future, which could take the forms of infusions or pills, said Dr. Jaehyuk Choi, one of the study authors and a dermatologist at Northwestern Medicine.
The study found that giving people with lupus anifrolumab, a drug that blocks interferon, prevented the T-cell imbalance that likely leads to the disease.
“We followed patients who received this as part of their clinical care and showed that in patients who got the drug, this cell imbalance was fixed or was on the way to getting 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 major challenge to developing a new treatment, according to Choi, is finding ways to administer it without activating aryl hydrocarbon receptors throughout the whole body, which may result in more side effects.
Even if such a treatment becomes available, Buyon said, it’s unlikely to work for everyone with lupus.
“We have come to the profound understanding that one drug will not do it all,” she said.
All bloods negative
GPs
Could this be my lupus or something else
A lot of people are scared of the word " chemo. .has anyone had it for lupus?
