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September 14, 2022

Unmasking Lupus: The Great Masquerader

Hayley Waterman was in college when her mom was diagnosed with a mixed connective tissue autoimmune disease.

“It’s similar to lupus but even more vague in definition,” Hayley says. “I took an immunology class to better understand what was going on with my mom and realized how cool the immune system is.”

Hayley Waterman
Hayley Waterman, Graduate Student

Fast forward a few years: Hayley is now a doctoral candidate in Molecular and Cellular Biology at the University of Washington. She is still fascinated with the immune system. Her research in BRI’s Hamerman Lab aims to better understand the cells and processes that lead to diseases like lupus.

Sometimes called “the great masquerader,” lupus is a complex disease that’s difficult to diagnose. People experience a wide range of symptoms, and the same treatment can affect people differently.

“There’s still so much we don’t understand about autoimmune diseases,” Hayley says. “Learning more about the underlying cells and processes in conditions like lupus can help us better understand the disease overall.”

Why Antibodies Attack in Lupus

Hayley’s research focuses on tiny proteins called antibodies, which recognize and tag bits of virus DNA. These tags tell other cells to start attacking. But in lupus, antibodies tag bits of your own DNA, and the immune system starts responding as if it were a virus.

Hayley is zeroing in on two types of antibodies called immunoglobulin A (IgA) and immunoglobulin G (IgG). Scientists already know that IgG plays a role in lupus. Hayley wants to know: Does IgA play a role in starting the disease? Does it make disease worse? And do IgA and IgG together create even more inflammation?

“You could think of IgA as firefighters and IgG as EMTs,” Hayley says. “They’re both called in when there’s a fire, but they have different jobs. I’m working to understand why these antibodies show up when there’s no fire.”
Using donated blood samples from people with lupus, Hayley created a model that allows her to study IgA individually and IgA and IgG together. So far, she has found that having both IgA and IgG leads to more inflammation. She’ll continue to collect data throughout the year and as she finishes her PhD.

Different Forms of Lupus

Hayley is also interested in how different antibody responses may lead to different manifestations of lupus.

“There’s so much diversity in lupus, it could probably be broken down further into different diseases,” Hayley says. “Better understanding the cellular mechanisms could help further categorize people and eventually lead to better, more personalized lupus treatments.”

Donor Samples Fuel Research

Hayley plans to continue autoimmune disease research after her PhD. She has enjoyed getting firsthand experience and mentorship with Jessica Hamerman, PhD, and her team. Conducting fundamental research with a strong focus on human disease and easy access to human samples have been some of Hayley’s favorite parts of working at BRI.

“I just want to thank all of the people who donate samples to our research. We really couldn’t do this without them,” she says. “Oftentimes, I’ll email the research team and ask if they can bring people back in to give additional samples. And most of the time people say yes — and that’s really incredible.”

Featured Bio Jenn Cole

Why Jenn Participates in Lupus Research

When Jenn Cole broke her wrist at age 10, it wasn’t healing properly. Her doctors said she had way too much inflammation and ultimately learned that she had juvenile rheumatoid arthritis. She was 13 when she got her second autoimmune disease diagnosis: lupus.

Now in her 30s, Jenn receives care at Virginia Mason and was excited for the opportunity to donate blood to BRI’s lupus research.

“It was great to do something that might aid in new treatments or help scientists better understand disease processes of lupus or any autoimmune disease,” she says.

Fatigue is the biggest way lupus impacts Jenn’s life. As an occupational therapist, she balances her time between clinical work, consulting and teaching — creating time to care for herself and her patients. She hopes that schools and workplaces continue to reduce stigma and create space for people with lifelong diseases, and that new treatments continue to arise.

“I’m not sure if treatments will drastically change in my lifespan, but I’d love to help make a difference for future generations — particularly because lupus often starts in young adulthood at such a formative time,” Jenn says. “I hope research leads to new treatments that allow people to just live their lives and not have to plan everything around their disease.”

Full-Width 3D Biological Antibody Immunoglobulin

Immunology 101: What is an Antibody

Antibodies are Y-shaped proteins. They tag or identify germs like viruses and bacteria. Antibodies are very specific; they each tag only one germ. For example, when you get your COVID-19 shot, this helps your body create antibodies that recognize COVID-19. If the virus enters your body, these antibodies can quickly recognize and tag it and tell other immune cells to destroy it.

In autoimmune diseases, your body mistakenly makes antibodies to your own tissue. This means they tell other immune cells to start attacking when there's no virus or bacteria. BRI's Hayley Waterman is studying who two types of antibodies tag healthy cells in lupus when there is no harmful invader.

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