Blog Main Image - People Men Hands Multiple Screens
January 5, 2022

Understanding Down Syndrome and Autoimmunity

You’ve probably heard of Down syndrome. You may even remember that it’s caused by an extra copy of chromosome 21. But fewer people know that almost half of those with Down syndrome have an autoimmune disease. Or that they are at lower risk of solid tumor cancers like breast cancer.

Bernard Khor

This means there’s something different about their immune systems. But no one knows exactly which differences are important or what to do about it. For years, BRI’s Bernard Khor, MD, PhD, has been working to learn more, aiming to improve the health of people with Down syndrome and explore what these immune system differences can teach us about autoimmunity.

“We’re building the first atlas of the immune systems of people with Down syndrome to map out key differences,” Dr. Khor says. “This lets us ask which differences are driving disease and if we can target them to improve treatment.”

Findings from one recent study could inform flu and COVID-19 care for people with Down syndrome — and potentially lead to more targeted treatments for autoimmune disease in this population.

Building Better Tools

Dr. Khor’s vision was to create a highly detailed portrait of the immune systems of people with Down syndrome — including genes, cells, molecules and how they work together. But these efforts generate millions of data points. Dr. Khor’s key challenge was understanding which differences drive specific processes, like aging.

“Think about it this way,” Dr. Khor says. “One sample from one person is like a map of the world. But that map is broken up into five million pieces, put in a bag and shaken up. And we want to find and study the 500 pieces that make up Texas.”

The research team started with a traditional approach to sort this data.

“With the typical tools, you might ask for Texas and it may give you Dallas or all of the U.S.,” Dr. Khor says. “We needed more precise control over the data.”

So Dr. Khor teamed up with bioinformatician Gautam Goel, PhD, to build a new algorithm — a set of instructions for a computer to sort huge data sets into meaningful information.

“With our method, you can zero in on the equivalent of states, cities, zip codes, with complete control,” Dr. Khor says. “And once you have that, you can pose questions like ‘which therapy will help this person?’ or ‘is this person at risk for disease?’”

The Immune System at Every Age

Dr. Khor’s team started mining the data with their new algorithm. They looked at samples from:

• People with Down syndrome

• People without Down syndrome or autoimmune disease

• People without Down syndrome but with type 1 diabetes (T1D)

“Studying T1D would help us understand how the immune systems in people with Down syndrome resemble those of people who have autoimmunity and vice versa,” Dr. Khor says. “We chose T1D because people with T1D don’t take therapies that alter the immune system and because T1D affects adults and children, so we could collect data from various age groups.”

This enabled the research team to build immune clocks — detailed profiles of how the immune system changes with age. Applying these clocks to people with Down syndrome revealed that their immune systems looked five to 17 years older than someone of the same age who doesn’t have Down syndrome.

“This is crucial when you think about COVID-19 or the flu,” Dr. Khor says. “With COVID-19, we start to see worse complications around age 60. But in people with Down syndrome, we might see complications closer to 40. We generally start giving a high-dose flu vaccine around age 65. But maybe that should be earlier for people with Down syndrome.”

Dr. Khor and Cate Speake, PhD, plan to study high-dose flu shots for people with Down syndrome in 2022.

Real Life Impact

This research also led to another key finding: They found higher levels of a protein called IL-6 — a known driver of autoimmune disease — among people with Down syndrome. This is promising because therapies that target IL-6 to treat autoimmune disease already exist.

“We have different drugs to treat each autoimmune disease and we usually try them in a certain order based on what works for most people,” Dr. Khor says. “But most people don’t have Down syndrome. For people with Down syndrome, maybe that order should be different. Maybe we start with therapies that target IL-6. And that can lessen a person’s suffering. That’s real-life impact.”

Immuno-what? Hear the latest from BRI

Keep up to date on our latest research, new clinical trials and exciting publications.