A key mystery behind one of the most common autoimmune diseases may finally have an answer.
Researchers from Northwestern Medicine and Brigham and Women’s Hospital say they’ve discovered the underlying cause of lupus, which affects hundreds of thousands of people in the United States.
Scientists have long suspected that a person’s genetic predisposition or hormones may predispose them to lupus, and that environmental factors, such as a past viral infection or exposure to certain chemicals, may trigger the disease.
Now, The study was published Wednesday in the journal Nature The study points to an abnormality in the immune system of lupus patients and provides a clear pathway for how the disease develops.
“What we found was a fundamental imbalance in the types of T cells that lupus patients 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 made its discovery by comparing blood samples from 19 lupus patients with those from healthy people, finding that the lupus patients had too many of a certain T cell involved in damaging healthy cells, and too few of another T cell involved in repair.
At the heart of this imbalance are proteins called interferons, which help defend the body against pathogens. Scientists have known for years that lupus patients have too much type I interferon, but new research shows this problem is associated with several adverse outcomes.
First, too much type I interferon can block a protein called the aryl hydrocarbon receptor, which helps regulate the body’s response to bacteria and environmental pollutants.
Blocking this receptor prevents the production of T cells that help heal wounds in the skin, lungs and intestinal barrier, but it also stimulates the production of T cells that attack healthy cells and are involved in the production of autoantibodies that are a hallmark of lupus.
Rao said the theory could explain the majority of lupus cases.
“I think this is true for essentially all lupus patients,” he said.
But other experts questioned the idea that there is a single explanation for all lupus cases.
“This is very exciting research and very hopeful, but it may be too early to say for sure that this is the root cause of the disease,” said Mara Leonard Richard, director of scientific programs at the Alliance for Lupus Research, a private funder of lupus research that is providing grants to Rao’s work.
Because lupus symptoms are so varied and there are so many contributing factors, “it’s been very difficult to find a single root cause of the disease,” Leonard Richard says. “Of course, if this turns out to be what causes lupus, it would be an amazing, really wonderful thing for lupus patients.”
Dr. Gilles Bayon, director of the Rheumatology and Lupus Center at NYU Langone Health, said the theory needs to be tested in larger samples.
“How can we know until we have a prospective study of 100 patients?” said Buyon, who was not involved in the study.
The Centers for Disease Control and Prevention More than 200,000 in the United States As many as 1 million people have lupus, but the National Lupus Foundation says the total number is far higher. Approximately 1.5 million peopleApproximately 90% of lupus patients are women.
Common symptoms include extreme fatigue, joint pain and skin rashes. In rare cases, it can cause kidney or heart damage and a weakened immune system that makes it difficult for the body to fight infections. These problems can be fatal or life-threatening.
Lupus has historically been difficult to treat: Many current treatments broadly suppress the immune system, including helpful infection-fighting T cells, and some lupus patients do not respond to standard treatments.
Study author Jae-hyuk Choi, a dermatologist at Northwestern Medicine, said the new research suggests there may be better treatments in the future, such as in the form of a drop or pill.
Studies have found that giving lupus patients the drug anifrolumab, which blocks interferon, can prevent the T cell imbalance that can cause the disease.
“We followed patients who received this treatment as part of their clinical care and found that this cellular imbalance was corrected or was being corrected in those who received the drug,” Choi said.
The researchers also tested the effects of adding a small molecule that activates the aryl hydrocarbon receptor in blood samples from lupus patients and found that it limited the accumulation of disease-promoting T cells.
Choi said the biggest challenge in developing new treatments is finding a way to administer them without activating aryl hydrocarbon receptors throughout the body, which could cause more side effects.
Even if such a treatment were available, it’s unlikely it would work for everyone with lupus, Buyon said.
“We’ve come to a deep understanding that one drug is not a cure-all,” she said.
