AgBioResearch

EAST LANSING, Mich. — According to the American Autoimmune Related Diseases Association, as many as 50 million Americans may be living with an autoimmune disorder. Many of these remain undiagnosed and, without intervention, can worsen over time. Given current treatment options, however, even those being actively managed can be met with complications. 

Autoimmune diseases can affect individuals at any age and cause the body’s immune system to attack its own healthy tissues. While there are no known cures, most current management strategies involve symptom reduction through immunosuppressive medication, which can present its own challenges with harmful side effects. 

Some of the most common autoimmune diseases are type-1 diabetes, lupus, psoriasis and rheumatoid arthritis. 

With respect to disease prevalence, gender and ethnic background differences are significant. The National Institutes of Health (NIH) indicates that 78% of diagnoses are for women. Additionally, African Americans and Latino/a populations are disproportionately affected. 

With lupus, which can damage several parts of the body including joints and organs, this gender and ethnicity disparity is even greater. The Lupus Foundation of America reports that 90% of those living with the disease are women of childbearing age, and African American women are three times more likely to develop lupus than white women. 

While autoimmune diseases are on the rise, according to NIH, many of them remain understudied. Researchers know that causes include genetics and environmental triggers, but relatively little progress has been made on mitigation techniques that cause less side effects and are more cost-effective. 

James Pestka, a University Distinguished Professor at Michigan State University, has dedicated his career to understanding more about the causes of — and potential alternative treatments for — autoimmune diseases, particularly lupus.  

“Autoimmune diseases such as lupus have a devastating effect on many individuals, and while there have been advancements in treatment, we still have substantial knowledge gaps,” Pestka said. “The goal of my research program is to understand how we can supplement — through actions like dietary changes — or even replace medications that, while effective, are currently either inaccessible to many people due to cost or present several adverse side effects.” 

Pestka also holds the title of Robert and Carol Deibel Family Endowed Professor with dual appointments in the Department of Microbiology, Genetics & Immunology, and the Department of Food Science and Human Nutrition. The endowed position has provided a steady funding source for his research program, in addition to several competitive grants. 

For years, Pestka has studied how those employed in professions such as construction, manufacturing and mining are more readily exposed to crystalline silica, an environmental toxin linked to lupus and other diseases. 

With funding from the National Institute of Environmental Sciences and the Lupus Foundation of America, Pestka and his team used a mouse model and found that consuming the omega-3 fatty acid docosahexaenoic acid, commonly known as DHA, can prevent activation and progression of lupus when caused by toxin exposure. DHA and other omega-3 fatty acids are produced in marine algae and abundant in cold-water fish. 

Recently, Pestka has partnered with three MSU colleagues to explore the ways in which these toxic particles induce inflammation and autoimmunity. Researchers include Jack Harkema, a University Distinguished Professor in the Department of Pathobiology and Diagnostic Investigation (PDI), and the Albert C. and Lois E. Dehn Chair in Veterinary Medicine; James Wagner, an associate professor in PDI; and Andrew Olive, an associate professor in the Department of Microbiology, Genetics and Immunology. 

Using mice, in addition to a cell culture model, the research team has shown that exposure to crystalline silica triggers autoimmunity and inflammatory responses in lupus-prone female mice. While researchers understand that DHA blocks this trigger, they will conduct further tests to understand how. The team will also examine how bacterial infections contribute to autoimmunity. 

“Revealing the mechanisms DHA uses to block those autoimmunity triggers can bring key insights into how it can be used in the future to stop flare-ups and progression of autoimmune diseases,” Pestka said. “I think this type of interdisciplinary work is critical to solving complex problems such as autoimmunity. My collaborators are experts in air pollution and chronic disease, so we all bring a different and valuable perspective to the table.” 

Olive said his work with Pestka has been extremely rewarding, noting the potential outcomes of the research. 

“The projects with Dr. Pestka are some of the most collaborative and impactful research I have participated in,” he said. “Understanding how environmental contaminants such as silica, as well as bacterial infections, contribute as triggers of autoimmunity is essential to determine how these diseases manifest. But even more importantly, our collaborative work using omega-3 fatty acids is providing possible therapeutic avenues that may help lupus patients who are limited to taking drugs with bad side effects. This mix of fundamental and translational research helps drive our productive collaboration, and we are excited about where these projects may lead.” 

Building on this foundational work, newly published research from Pestka in Frontiers in Immunology has shown promising results for DHA therapies in a group of more than 400 individuals from the Michigan Lupus Epidemiology and Surveillance Cohort. 

Co-authors of the study include Jenifer Fenton, a professor in the MSU Department of Food Science and Human Nutrition, and Emily Somers, a professor in the University of Michigan Medical School and the School of Public Health. 

The research focused on patients with lupus nephritis, a severe condition that alters kidney function and can lead to kidney failure. The group examined associations between concentrations of various fatty acids in blood and patient-reported outcomes on disease activity, pain and sleep quality. The study showed DHA led to improvement in all three areas, whereas higher levels of saturated and monounsaturated fats found in ultra-processed foods were associated with poor outcomes. 

“Many people living with lupus actively seek dietary supplement alternatives to potentially toxic medications, and this research offers clear guidance on how supplements, such as omega-3 fatty acids, can be integrated into holistic disease management,” said Joy Buie, vice president of research for the Lupus Foundation of America. “These findings provide renewed hope for patients aiming to reduce their reliance on more toxic treatments and ultimately improve their overall quality of life.”

Pestka said the team has also found that omega-3 fatty acids at human-equivalent doses that cost $1 to $2 per day mimic the effects of biological therapies costing thousands of dollars per month. 

“We’re seeing that consuming omega-3 fatty acids in dietary additions or through supplements can be a way to lessen the inflammatory symptoms of autoimmune diseases,” Pestka said. “Used by themselves or in combination with smaller doses of immunosuppressing drugs, these omega-3 fatty acids may help patients avoid some of the harsh side effects of the drugs and improve quality of life. We’re looking to help patients enter the maintenance stage more quickly and reduce the possibility of flare-ups.

“One of the other important aspects of this research is that the source of omega-3 fatty acids is sustainable. Algal cultures are a way to produce this product in a way that can keep costs low, prevent overfishing and make the product accessible to those who need it.” 

Michigan State University AgBioResearch scientists discover dynamic solutions for food systems and the environment. More than 300 MSU faculty conduct leading-edge research on a variety of topics, from health and climate to agriculture and natural resources. Originally formed in 1888 as the Michigan Agricultural Experiment Station, MSU AgBioResearch oversees numerous on-campus research facilities, as well as 15 outlying centers throughout Michigan. To learn more, visit agbioresearch.msu.edu.