What goes wrong in the immune system that causes autoimmune disease or limits its ability to fight infections? That’s the question Bernard Khor, MD, PhD, started with 12 years ago. His search for answers led him somewhere unexpected: to people with Down syndrome. 

“Our early research showed that a gene on the 21st chromosome might play a role in throwing the immune system out of balance,” Dr. Khor says. “Because people with Down syndrome have an extra copy of the 21st chromosome, they have an extra copy of that gene. So we wondered if people with Down syndrome would have higher rates of immune system disease. If so, it’s additional proof that this gene plays a key role in these diseases.”

They were right: Scientific literature showed people with Down syndrome are four to six times more likely to have autoimmune diseases like celiac and Type 1 diabetes. People with Down syndrome are also about 10 times more likely to die of a respiratory infection. 

This inspired Dr. Khor to learn how and why Down syndrome impacts the immune system. He recently earned a $3.5 million grant for this research. He aims to better understand the immune system overall and to ask targeted questions like how Down syndrome impacts vaccine response. 

“This research can help improve health for people with Down syndrome and teach us some universal truths about aging, autoimmunity and the immune system overall,” Dr. Khor says.

Two Big Questions: How and Why

Dr. Khor’s previous research found that the immune systems of people with Down syndrome look between 5 and 17 years older than someone of the same age without Down syndrome. 

“This is really important when we think about COVID-19,” Dr. Khor says. “A 50-year-old with Down syndrome’s immune system might look more like that of a 70-year-old without Down syndrome. And that means a much higher risk of complications.” 

This new grant will allow him to dive deeper into this work, examining exactly how and why the immune system changes with age. This includes looking at the immune system broadly and zeroing in on areas of interest, such as if certain immune cells become less active as we age. 

“Learning more about exactly how the immune system changes as we age allows us to answer a crucial question: What can we do about it?” Dr. Khor says. “Can we restore healthy responses, in people with Down syndrome or older individuals without Down syndrome? If so, it could improve the quality of life for a lot of people.”