0505-Feature-CVGPS Series 05_Blog

Editor’s Note: This is the fifth in a series of stories explaining how the scientific research underway in the Cardiovascular Genome-Phenome Study can save and improve lives.

The immune system does a lot of things. It protects the body from infections. It makes vaccines work.

It can juggle these tasks because of the body’s roughly 100 billion B cells, each programmed to make a specific antibody protein that recognizes a specific foreign invader, like the flu virus. So if this large population of B cells becomes less diverse for some reason, you get holes in the armor or gaps in the ranks. That means the immune system might not work as well.

Ramy Arnaout, M.D., D.Phil, is an expert in the emerging field of immunomics, which looks at millions of antibodies and T cells using cutting-edge technology. Preliminary observations in people have led Arnaout and his research team to believe that when the immune system isn’t working well, it can lead to chronic inflammation, which contributes to heart disease, the No. 1 killer of Americans.

The immune system’s B cells and T cells play important roles in vaccination, infection, autoimmunity and cancer. Mounting evidence suggests the same is true in cardiovascular diseases.

Arnaout, associate director of the Clinical Microbiology Laboratories at Beth Israel Deaconess Medical School and an assistant professor of pathology at Harvard Medical School, was recently awarded $500,000 to conduct research as part of the American Heart Association’s Cardiovascular Genome-Phenome Study. His team will analyze the antibody repertoires of more than 1,000 white, black, Hispanic and Asian people to clarify the link between antibodies, cardiovascular diseases and aging.

Arnaout talked recently with AHA News about his research.

If your theory pans out that a poorly functioning immune system can lead to inflammation, what could that mean for the future of heart disease? “If we’re right, it might give us a new way to assess your risk of heart disease, which is information that lets you and your doctor take steps to keep it at bay. And we just might have a new tool for our prevention toolkit: keeping up your antibody diversity.”

Why does this diversity matter so much? “Having a diverse immune repertoire is like having a diverse workforce. Think back to how people got around 100 years ago. Some folks had cars and some still had horses. So as far as workers go, some worked on assembly lines and at gas stations, while others made bridles, saddles and horseshoes. Whether you had a car or a horse, you could find what you need. Today, of course, it’s pretty much all cars. But what if we suddenly had to go back to horses? We’d be in trouble.

We could try to transition the workforce from assembly lines back to smithies, but it would be messy. Your horse would throw a shoe or a rider, causing all kinds of problems. This hurts not just you and the horse, but everybody. The idea is that the loss of diversity in the immune repertoire contributes to heart disease in a similar way.”

What excited you about the field of immunomics? “I trained in medicine but also mathematics, in a field called theoretical biology. It involves translating ideas into equations and using math to sort out the implications of those ideas. It’s how Spock or Data from Star Trek would do biology. It struck me how fundamental some of the implications were that followed from differences in scale, size and time between people and all the things that can make us sick.

It turns out size matters. In the grand scheme of life, people are big and reproduce slowly. Viruses, bacteria and cancer cells are small and reproduce quickly — which means they can adapt to our defenses a lot faster than we can adapt to their attacks. So how do we stay ahead? We’ve got our own little fast-adapting task force of B cells and T cells.

B cells are true masters of adaptation. For example, if a B cell equipped to attack the flu encounters a flu virus in the body, it not only divides to make more copies, but the copies get tweaked to become even better at fighting the flu.

The potential for diversity is just stunning, with the 100 billion or so B cells in your body able to target possibly millions of different potential attackers. When I realized that technology might make it possible to know what all these cells are doing, and that there were even broader implications for things like heart disease, I knew that immunomics was where I wanted to be.”

What do you expect to find? “That lower B-cell repertoire diversity carries an increased risk of heart disease and death. Beyond that, we are excited to see what surprises we find. When you do something new, you don’t have the benefit of an instruction manual — you’re writing the playbook as you go. That’s why we’ve spent a lot of time building specialized tools to make sure we’re doing it right.”

Why should people care about heart disease and the research that’s being done to support treatment advances? “Heart disease might not be the shiniest new thing, but as the leading cause of death for Americans and much of the rest of the world, it remains vitally important. To borrow a phrase, you might not be interested in heart disease, but heart disease is interested in you.”

Read about the other studies in this series.