Researchers Take a Multifaceted Approach to Understanding Autoimmune Disease Disparities

The disproportionate rates at which some autoimmune diseases strike African American women are among the most glaring disparities in medicine. About 90% of people with lupus and 60% of those with scleroderma are women and the majority identify as African American or Hispanic.

Paula S. Ramos, Ph.D., and Diane Kamen, M.D., have spent decades trying to identify the causes for these striking inequities and recently received funding from the National Institutes of Health for a novel study investigating how social factors might influence lupus in African American women through epigenetic changes. “Many studies analyze biospecimens but not social factors, or they collect social data but not biological samples,” says Ramos. “For each participant, we’re collecting genetic data from blood samples as well as social exposure data, including sociodemographic, behavioral, racial discrimination, and social support data.” The study will also consider disease severity, comorbidities, and outcomes.

It is well established that genetic risk factors can increase vulnerability to developing certain diseases. It is also known that social factors such as housing instability, racial discrimination, poverty, trauma, and violence impact disease development. “What we don’t know,” says Kamen, “is how these things interact to affect our biology and influence disease development or severity. Why do some people develop autoimmune disease while others with similar environmental exposures and genetics do not? Can we identify environmental or genetic protective factors to help prevent people at risk from developing lupus or reduce their disease severity?”

They chose to study lupus, not only because African American women have more severe disease and worse outcomes, but also because it is a prototypical autoimmune disease. “It’s the mother of all autoimmune diseases,” explains Kamen. “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. 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.”

Lupus is also highly unpredictable, frustrating patients who often live on a roller-coaster of flares and remissions as well as healthcare providers who must frequently adjust treatment to keep it at bay. Even getting a correct diagnosis can be challenging. “Lupus onset can be insidious. It can come on very slowly,” says Kamen. “Some people go years with non-specific symptoms before someone finally puts it together as lupus and gets them the right treatment. Unfortunately, some people already have scarring from chronic inflammation before they get a correct diagnosis.”

Both Ramos and Kamen agree that if their study can help explain how multiple social factors influence lupus, it will be a great step forward. “We’re measuring DNA variation, DNA methylation, and gene expression at the genome-wide level in the major immune cell types such as T-cells, B-cells, and monocytes. We want to understand how social factors like racial discrimination affect lupus outcomes through epigenetic changes, taking into account genetics and other sociodemographic factors. We’ll specifically look at the effects of social factors on DNA methylation and gene expression,“ explains Ramos. “We can then compare to see if differences in gene expression are associated with social factors. For example, do participants who report more racial discrimination have different gene expression patterns than those who report less?”

Unravelling associations among so many overlapping risk factors is a daunting analytical challenge, but the crux of their work is its human face. Without the participation of African American women with lupus, their project would go nowhere. “We want to make sure study participants and the broader African American community are included and feel this project is of value to them,” says Ramos. “Often, in historically marginalized populations, researchers collect samples for study but don’t give participants feedback on what they found or request feedback on research directions. The people who made the research possible are not included as partners in the research.”

Fortunately, other MUSC researchers, including the late Ida Spruill, Ph.D., have laid a strong foundation for community-based, participatory research in South Carolina’s coastal communities. In the 1990s, they began holding regular meetings with community members to talk about proposed and ongoing studies, community priorities, and how study results are relevant to their daily lives.

“Over twenty years ago, Ida Spruill helped form a community-based Citizens Advisory Council to help endocrinology researchers from MUSC study why diabetes disproportionately affected African Americans in the Sea Islands around Charleston,” says Kamen. “Dr. Gilkeson and I went to a community advisory board meeting back in 2002 and talked about how lupus, like diabetes, was also a chronic disease with higher morbidity and mortality in their community. They were very open to helping us. One woman on the board actually had lupus and another had a relative who died of it. So, they were very aware of its impact and welcomed us with open arms. It was the beginning of a wonderful, trusting, collaborative relationship that we’re still involved in today–thanks to Dr. Spruill’s really visionary work.”

While they acknowledge that it is an ambitious project, Ramos and Kamen think that understanding how social factors affect gene regulation and how the resulting gene expression patterns affect lupus, could turn up insights that may open new avenues 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,” says Ramos.

“Doing something to reduce the disparities we see in clinic is what makes me eager to go to work every day,” says Kamen. “To help figure out how potentially modifiable factors influence the development of autoimmune diseases like lupus that have terrible impacts on patients, their families, and the broader community.”

Article by Kat Hendrix, Ph.D.