Lupus is an autoimmune disease that can affect women nine times more often than men, often turning up in women in their 20s and 30s. It can cause joint pain, rashes, fatigue, and damage to organs — especially the kidneys. The root cause is still unclear, but it may have to do with genetics.
“[Lupus] can cause injury to a number of different organs, all mediated by this particular autoimmune process,” says Deepak Rao, a rheumatologist at Harvard Medical School.
New research is improving doctors’ understandings of how lupus hijacks the immune systems of patients and could lead to a new treatment that targets the pathways involved in the autoimmune disease.
“Lupus is difficult to diagnose, difficult to treat, with therapies that aren’t exceedingly effective in many patients,” says Rao.
What Is Lupus?
Researchers know that lupus is an autoimmune disease – it does damage to the bodies of patients not by shutting the immune system down, but by convincing it to work on override, attacking the bodies and organs of those who suffer from it. But scientists still don’t know the specific ways in which the disease works. Rao and his colleagues wanted to take a closer look to find the pathway.
“We’ve been looking for features of immune activations to characterize this disease,” he says.
In a study published recently in Nature, the team examined the blood cells of volunteers infected with lupus as well as blood from non-infected people.
They analyzed the blood using mass cytometry, a technique that allowed them to quantify the different types of immune cells in the blood. They compared the immune cells in the blood of lupus patients with those who didn’t have lupus.
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Researchers Identify How Cells Interact in Lupus Patients
They found several differences, one specifically in the type of T cell. T cells typically work with another type of immune cell called B cells. B cells produce antibodies, which help ward off infection most of the time. But when B cells produce certain types of antibodies that bind to molecules made by our own cells, known as autoantibodies, researchers have found that they can cause injury in patients with lupus.
Rao and his colleagues identified CD4 T cells — or pathogenic T cells — as the ones causing an imbalance of B cells. To better understand why, they used the gene-editing tool CRISPR in test tubes to disrupt the genes expressed by these T cells. That way, by process of elimination, they could figure out the culprit.
This CRISPR technique revealed that loss of a protein called the aryl hydrocarbon receptor (AHR) caused T cells to become more pathogenic and increase their interactions with B cells.
They also found that interferon, another type of protein known to be involved in lupus, inhibits the AHR signaling process in lupus patients.
Read More: CRISPR Gene-Editing Technology Enters the Body
Potential Therapies and Treatment for Lupus
This study is just a first step to better understand the how lupus works. And Rao says they can use this knowledge to find a better way to interrupt this harmful process in people with lupus.
“The idea for a new therapy in lupus is to design a drug that activates AHR,” he says. “By activating AHR, we would suppress the development of pathogenic T cells.”
There is currently a drug on the market that helps to activate AHR. The team tried this with in vitro studies in the lab, but the drug had too much potential toxicity and side effects like diarrhea, headaches, and upset stomachs to be allowed for actual patients.
Rao says that they hope to find a drug that more specifically just activates AHR in T cells without so many negative side effects.
Article Sources
Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:
Rheumatologist at Harvard Medical School. Deepak Rao
Nature. Interferon subverts an AHR–JUN axis to promote CXCL13+ T cells in lupus
Joshua Rapp Learn is an award-winning D.C.-based science writer. An expat Albertan, he contributes to a number of science publications like National Geographic, The New York Times, The Guardian, New Scientist, Hakai, and others. Find him on Instagram.
