A major mystery behind one of the most common autoimmune diseases may finally be solved.
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 United States.
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, such as a previous viral infection or exposure to certain chemicals.
A study published Wednesday in the journal Nature outlines a clear path for how the disease develops and points to abnormalities in the immune systems of people with lupus.
“What we found was a fundamental imbalance in the types of T cells that patients with lupus 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 an important role in the body’s immune response.
The study reached its findings by comparing blood samples from 19 people with lupus with those from healthy individuals. The comparison showed that people with lupus had too many of a certain T cell associated with damage to healthy cells and too few 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 years that people with lupus have excess type I interferon, but the new study links the problem to a variety of adverse 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 blocks the production of T cells, which can help heal wounds in the skin, lungs, and intestinal barrier. It also stimulates the production of T cells, which attack healthy cells and play a role in the formation of autoantibodies, a hallmark of lupus.
Rao said the theory could explain the vast majority of lupus cases.
“I think this will be true for essentially all patients with lupus,” he said.
But other experts have questioned the idea that there is a single explanation for all cases of lupus.
“This is very exciting and very promising research, but it may be too early to say that this is 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 provided grant funding for Rao’s study.
Because lupus symptoms are so diverse and the contributing factors are so varied, “it’s been very difficult to find a single root cause of the disease,” Lennard Richard says. “Frankly, if this turns out to be the cause of lupus, that would be incredible and really wonderful for people living with lupus.”
Dr. Jill Buyon, director of the rheumatology division and Lupus Center at NYU Langone Health Center, said the theory needs to be tested in a larger sample.
“How will we know unless they look at 100 patients prospectively?” 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 United States have lupus, but the Lupus Foundation of America puts the total number much higher: about 1.5 million. About 90% of people with lupus are women.
Common symptoms include extreme fatigue, joint pain, or skin rashes. In rare cases, the disease can cause kidney or heart damage or weaken the immune system, making it harder for the body to fight infections. These problems can be fatal or life-threatening.
Lupus has historically been difficult to treat. Most current options largely suppress the immune system, including the beneficial T cells that fight infection. And for some people with the disease, standard treatments are not effective.
Dr. Jaehyuk Choi, a dermatologist at Northwestern Medicine and one of the study’s authors, said the new study points to the possibility of better treatments in the future, which could come in the form of infusions or pills.
The study found that giving lupus patients anifrolumab, a drug that blocks interferon, prevented the T cell imbalance that is likely to lead to the disease.
“We followed patients who received this drug as part of their clinical care and showed that this cell imbalance was corrected or on the way to being corrected in patients who received the drug,” 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 this limited the accumulation of disease-promoting T cells.
The biggest challenge in developing a new treatment, Choi said, is finding ways to deliver the treatment without activating aryl hydrocarbon receptors throughout the body, as this could lead to more side effects.
Even if such a treatment were available, it’s unlikely it would work for everyone with lupus, Buyon said.
“We have come to a deep understanding that no single drug can do everything,” he said.
This article was originally published on NBCNews.com