Understanding how viruses impact the immune system has long been a focus at BRI. Two years of pandemic life have made answering two questions particularly important: Can respiratory viruses like the common cold or COVID-19 start the chain reaction that leads to immune system disease? Can they make conditions like asthma, allergies or rheumatoid arthritis (RA) worse?
A 5-year, $11.4 million grant from the Human Immunology Project Consortium (HIPC) will enable Carmen Mikacenic, MD, and Matt Altman, MD, MPhil, to dive into these questions. They’ll each study around 250 people who have immune system diseases linked with higher risk for complications from respiratory viruses. Dr. Mikacenic will study adults with RA while Dr. Altman will follow children with asthma and allergies.
“By studying different populations with the same method, we can move toward a broader understanding of immune response to viruses across age groups, backgrounds and chronic diseases,” Dr. Altman says. “We should gain more insight into patterns we already know about and learn more about parts of the immune system we don’t really understand.”
At the beginning of the study, researchers will collect vast amounts of data including blood samples, breath samples and nasal swabs. If participants get a virus, they’ll give additional samples. The research team will examine these samples to see how the immune system changes when infected with a virus. Eventually, this information will be available to scientists across HIPC.
“This study will help us better understand what’s going on in the immune systems of people who are at risk for complications, and how viruses may lead to or worsen immune system disease,” Dr. Mikacenic says. “For other scientists, this data could also provide insight into everything from pediatric asthma to T cell response to vaccination.”
Lung Inflammation in RA
When most people think about RA, they think about joint problems. But RA can also impact the lungs.
“A troublesome feature of RA is that some people develop airway disease that looks similar to asthma. The inflammation and scarring make it harder and harder to breathe,” says Dr. Mikacenic, a physician-researcher who focuses on lung disease. “Often, their lung disease is quite severe by the time they get to my office. We can treat the inflammation, but this doesn’t get to the root of the problem, which is that their immune cells are attacking the lungs.”
The research team will study people recently diagnosed with RA and others who have had RA for a while to learn if, or how, the immune system response is different. They’re also hoping to learn more about whether respiratory viruses can make RA worse.
“When you get a virus, the body releases proteins to fight it off. But rather than just clearing the infection, it may stir things up and lead to more autoimmune disease activity,” Dr. Mikacenic says. “This study will allow us to learn more about if getting multiple respiratory infections when you have early RA eventually leads to worse disease in the joints.”
Dr. Mikacenic is particularly interested in learning if certain immune system characteristics can help predict who will develop severe lung disease from RA.
“If we knew who was most likely to develop lung disease, we might be able to find treatments that target the root of the lung problems or even keep them from happening in the first place,” she says.
Asthma, Allergies and Colds
When most kids get a cold, they’re sick for a few days and then they get better. But kids with allergies might get much sicker — and those with asthma may even experience asthma attacks as a result of the virus. Dr. Altman is working to understand why this happens and how to reduce their risk.
“Even when kids are mildly or moderately sick, these infections have a huge social burden. Kids miss school, parents miss work,” Dr. Altman says. “In serious cases, kids can die from asthma attacks and respiratory infections.”
Dr. Altman’s goal is to better understand exactly what’s going on with the immune cells in these children’s airways. This could ultimately help improve the health of kids with asthma and allergies by reducing their risk of complications from viral infections.
“Since there’s still no cure for the common cold, we need better strategies to prevent a common respiratory infection from triggering a health crisis,” Dr. Altman says. “Vaccines, treatments or prevention are all possibilities. Our work to map what is happening in the immune system is the first step.”
June 17, 2022
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