Addressing Rheumatology & Immunology Health Disparities

Rheumatology MUSCLE Group 2021
The MUSC Lupus Erythematosus research group (M.U.S.C.L.E.) is comprised of faculty and staff with interests in clinical, translational, and basic research related to lupus and community outreach to improve knowledge and awareness of lupus.

Improving Minority Health in Rheumatic Diseases

Jim OatesIn fiscal year 2022, the P30 Core Center for Clinical Research (Improving Minority Health in Rheumatic Diseases or IMHRD) was successfully renewed with Jim Oates, M.D. as the new lead. This center provides research resources to enable and enhance clinical and translational research on two autoimmune connective tissue diseases, scleroderma and lupus, that have a disparate impact on women and African Americans.

The center, initially led by Gary Gilkeson, M.D., was established in 2012 through a P30 center grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health. With the core purpose of improving minority health, IMHRD researchers place a major emphasis on communicating and collaborating with minority patient groups and communities to encourage input and participation in clinical research and health promotion activities.

DeAnna Baker Frost, M.D., Ph.D. - Expanding Expertise at the MUSC Scleroderma Center of Excellence

DeAnna Baker-FrostDeAnna Baker Frost, M.D., Ph.D., is an assistant professor in the Division of Rheumatology & Immunology with a clinical interest in autoimmune diseases and fibrosis. Along with her colleagues, Dr. Baker Frost recently published findings from her NIH-funded study on the link between estradiol levels and severe disease in scleroderma in “Arthritis Research & Therapy”. As a member of the MUSC Scleroderma Research Team, Dr. Baker Frost is continuing her efforts to improve patient lives through compassionate patient care and innovative research. She shares her insights into the diagnosis, treatment, and future of scleroderma – a rare autoimmune connective tissue disease that disproportionately affects women and underserved minorities, often profoundly affecting quality of life and survival.

Estradiol is one of the forms of estrogen that naturally occurs in our body. Males and post-menopausal females typically have lower levels of estradiol. “However, we found that in scleroderma patients, men and post-menopausal females have higher levels of estradiol compared to those without scleroderma,” said Dr. Baker Frost.

Estradiol can also promote fibrosis, which is one of the hallmarks of scleroderma.

“Therefore, we are concerned that these high levels of estradiol are contributing to fibrosis,” said Dr, Baker Frost. “We are completing other experiments to better understand how these high levels influence the severity of scleroderma in patients. But it is possible that using medications that prevent high levels of estradiol may be a treatment option for patients.”

According to Dr. Baker Frost, the current thought is that genetics does play a role in the development and possibly the severity - in several autoimmune diseases, including scleroderma, but we need more research in this area. “With increased resources and collaborations dedicated to scleroderma research, the hope is that one day this disease can be cured,” said Dr. Baker Frost.

Researchers Take a Multifaceted Approach to Understanding Autoimmune Disease Disparities

L-R: Diane Kamen, M.D., Quinette King, and Paula Ramos, Ph.D.
L-R: Diane Kamen, M.D., Quinette King, and Paula Ramos, Ph.D.

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 years 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 Dr. 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 Dr. 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?”

Both Drs. 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, accounting for genetics and other sociodemographic factors. We’ll specifically look at the effects of social factors on DNA methylation and gene expression,” explains Dr. Ramos. “We can then compare to see if differences in gene expression are associated with social factors.”

While they acknowledge that it is an ambitious project, Drs. 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.

Adapted from original article by Kat Hendrix, Ph.D.

Sex Bias in Autoimmune Disease

Melissa Cunningham, M.D., Ph.D.Systemic lupus erythematosus (SLE) and many other autoimmune diseases disproportionately affect females. Researchers in the lab of Melissa Cunningham, M.D., Ph.D., have a particular interest in autoimmunity, inflammation, and sex bias. Dr. Cunningham’s team investigates the role of estrogen receptor alpha (ERα) in modulating the inflammatory response, with a specific focus on protective ERα _variants. They use mouse models of lupus and patient samples to study ERα _modulation of inflammation in innate immune cells. In recent years, the team has discovered that if they removed ovaries from lupus mice expressing an ERα _short variant, and gave the animals estrogen, mice were protected from developing severe kidney disease.

Although the exact mechanism of its protective effect is currently unknown, Dr. Cunningham’s team hypothesizes that the ERα _short variant regulates the immune response similar to a short endogenous ERα _variant that is expressed in both mice and humans. The team proposes this short ERα _as a novel therapeutic target in lupus and has recently expanded their studies to look at selective estrogen receptor modulators (SERMs) that may act similarly and could be used in humans as an adjuvant treatment strategy.