It’s an unheralded fact: Of the 24 to 50 million Americans with an autoimmune disease, like lupus or multiple sclerosis, 80% are women. And a disproportionate number of them are Black.
Now, scientists at Stanford University have found that a faulty genetic molecule could be responsible for the immune system misidentifying healthy tissue as a threat. The breakthrough study, published earlier this year, could lead to better treatments for the millions who battle these chronic diseases.
“Our study shows that you do not need female sex hormones. You don’t even need a second X-chromosome” to develop an autoimmune disease, says Howard Chang, a dermatologist and molecular geneticist at Stanford University School of Medicine in California. The molecule, called Xist, “could have a major role in developing some autoimmune diseases” by itself, he said.
Researchers are also investigating how socioeconomic, environmental, and epigenetic factors may play a role in these diseases.
“The disproportionate rates at which some autoimmune diseases strike African American women are among the most glaring disparities in medicine,” says Paula S. Ramos, a geneticist and associate professor at the Medical University of South Carolina. “About 90% of people with lupus and 60% of those with scleroderma are women, and the majority identify as African American or Hispanic.
“Many studies analyze biospecimens but not social factors, or they collect social data but not biological samples,” Ramos adds.
Autoimmune diseases occur when the body’s immune system attacks its own healthy tissues and cells, mistaking them for harmful invaders. Severe cases like lupus, rheumatoid arthritis, and Type I diabetes can lead to chronic inflammation, pain, and damage to organs or systems.
While the exact causes remain unclear, autoimmune diseases are believed to arise from a mix of genetic predisposition, environmental triggers, and immune system dysregulation.
The research suggests women are affected more often because the Xist (pronounced exist) molecule fails to turn off critical functions in a woman’s two X chromosomes.
The Xist molecule can trigger an unwanted immune response. Since most autoimmune diseases are most often diagnosed in adults, the sex hormones that show up after puberty — chiefly testosterone and estrogen — are believed to play roles. But some researchers suspect socioeconomic factors could also be a factor.
The breakthrough raises hope that better medicines could be developed to treat these diseases by targeting the specific molecule. Current treatments and medications affect the entire immune system, which causes an intense range of side effects.
Women are 10 times more likely to contract lupus than men and 20 times more likely to develop Sjögren’s syndrome, an illness that causes extreme dryness of glands in the eyes and mouth.
Although autoimmune diseases affect Black women at alarmingly disparate rates, and often advance more quickly than in patients from the overall population, very little research into these diseases includes Black people.
Ramos and Dr. Diane Kamen have researched the causes of stark inequities in these diseases and investigated how social factors might influence lupus in African American women.
African American women with lupus have more severe cases and worse outcomes than women in other demographics. Lupus provides the perfect example of how all autoimmune diseases function.
“It’s the mother of all autoimmune diseases,” Kamen says. “The basis of autoimmune disease is that the immune system attacks healthy cells and tissues, and many are focused on one area of the body.”
“For example, MS (multiple sclerosis) attacks the nervous system, and RA (rheumatoid arthritis) attacks the joints,” she says. “But antibodies from lupus attack many different types of cells in many different parts of the body. Patients can have multiple different organ systems affected at the same time.”
Ramos says each participant in her research will submit genetic data from blood samples “as well as social exposure data, including sociodemographic, behavioral, racial discrimination, and social support data.”
Ramos and Kamen believe understanding how social factors affect gene regulation and how the resulting gene expression patterns affect lupus, could lead to new methods for helping patients.
“We hope to see some positive effects of things like social support that may offset detriments like racial discrimination or low socio-economic status,” Ramos says.
Jennifer Porter Gore is a writer living in the Washington, DC area.