The aging process deteriorates our immune system, but regardless of age, some people have a greater ability to fight all kinds of ailments. A recent example is the SARS-CoV-2 coronavirus infection, which caused millions of deaths and yet many of those affected were asymptomatic. Genetic and environmental factors and the interaction between genes and the environment – epigenetics – influence the response to disease, but the immune resilience es a key factor in longevity and it decisively influences mortality from HIV/AIDS, influenza, sepsis, recurrent skin cancer or COVID-19, according to new research.
The study was conducted by researchers at the University of Texas Health Science Center at San Antonio in collaboration with scientists from five countries and has shown that the ability to resist or recover from infections and other sources of inflammatory stress, called “immune resilience” It is very different in each individual. To verify this, these scientists developed a unique set of metrics that have allowed them to quantify the level of immune resilience.
Their findings have been published in Nature Communications and will help healthcare professionals make healthcare decisions and researchers understand the differences in length of life and health problems in people of similar ages, since although age influences the body’s response to inflammatory and infectious stressors, some people maintain or restore optimal immune resilience regardless of how old they are, has pointed out the Dr. Sunil K. Ahujaprofessor at UT Health Science Center San Antonio specializing in infectious diseases and first author of the paper.
Main benefits of immune resilience
“Immune resilience is the ability to maintain good immune function, called immunocompetence, and minimize inflammation while experiencing inflammatory stressors,” explained Dr. Dr. Weijing He, co-author and senior research scientist at the Veterans Administration’s Center for Individualized Medicine and the Veterans Administration Foundation for the Advancement of Veterans Health Research. “We found that during aging and when experiencing inflammatory stress, some people resist degradation of immune resilience.”
“Immune resilience is the ability to maintain good immune function, called immunocompetence, and minimize inflammation while experiencing inflammatory stressors”
Laboratory tests designed to assess levels of immune resilience were carried out on around 50,000 people of different ages and types of challenges to their immune systems, and the results showed that individuals with optimal levels of immune resilience were more likely to:
The researchers measured immune resilience in two ways: One was to measure the balance between CD8+ and CD4+ T cells, which are types of white blood cells which are responsible for fighting infections, but in many infectious and autoimmune diseases there is an imbalance in their levels. The balance between CD8+ and CD4+ T cells, divided into four distinct categories called grades of immune health, was measured in various infection cohorts and at all ages.
They also measured the expression levels of genes related to immunocompetence and a greater probability of survival compared to those related to inflammation and a greater risk of death. Gene expression markers signifying high immunocompetence and low inflammation were identified with the grade of immune health tracking optimal immune resilience.
“Many people think only of inflammation when considering disease outcomes,” said Grace C. Lee, a researcher at the VA Center for Individualized Medicine and an assistant professor at the University of Texas at Austin School of Pharmacy and a co-author. “However, the concept of immune resilience captures the levels of immunocompetence and inflammation together.”
Balance between immunocompetence and inflammation
The study exposes the novel concept of immune resilience, which looks at the balance between immunocompetence and inflammation as a decisive factor in health outcomes, regardless of age. “This is an advantage and a step forward because by looking beyond inflammation, we can discover new prevention and treatment strategies for chronic diseases such as cardiovascular disease, COVID-19, HIV/AIDS and cancer,” says Lee.
The researchers divided Framingham Heart Study participants into four groups based on gene expression markers of immune resilience and found that those “with optimal immune resistance, defined by gene expression markers signifying high immunocompetence and low inflammation , lived longer after controlling for the effects of age and gender,” said Muthu Saravanan Manoharan, MS, co-author and senior research scientist at the VA Center for Personalized Medicine and UT Health Sciences Center at San Antonio, who points out that, on the contrary, “Participants with metrics that meant low immunocompetence-high inflammation died earlierwhile those with a combination of high immunocompetence-high inflammation or low immunocompetence-low inflammation had an intermediate life expectancy.
Immune resilience and response to infection
In one of the cohorts, the authors observed a rare ability to maintain a high level of immunocompetence with a low level of inflammation despite chronic inflammatory stress, termed elite immune health. “Interestingly, we found that some young adults retained optimal markers of immune resilience despite HIV infection,” he said. Jason F. Okulicz, a US Air Force infectious disease physician and lead member of the study team. “The preservation of these markers associated with the resistance to developing AIDS and a low level of HIV in the blood. Surprisingly, we found that after starting antiviral therapy early, some people with HIV manifested markers of optimal immune resistance typically seen in younger HIV-negative adults.”
“Inflammatory stressors such as the flu can degrade the immune health of a vulnerable person in the long term”
The team also examined gene expression markers for immune resistance in a group of healthy college students and community members, all younger than 50, who had their blood drawn before the flu season began. On the day of their first symptoms, most participants, including those with optimal immune resistance before influenza infection, had gene expression profiles indicating low immunocompetence and high inflammation, which is seen in people with a shorter life.
Many people recovered their initial level of immune resistance; however, even some of those who had optimal immune resistance before influenza infection did not. “Six months after the flu, some people were still showing signs of poor immune health gene expression,” he says. Nathan Harper, senior biostatistician at the VA Center for Personalized Medicine and the Foundation for the Advancement of Veterans Health Research. “This is quite surprising, because it means that inflammatory stressors like the flu can degrade the immune health of a vulnerable person in the long term.”
In the case of COVID-19, they found that about 80% of people had poor immune health grades when presenting with acute COVID-19, and their immune grade predicted mortality, regardless of age. “Even among patients with severe community-acquired pneumonia and sepsis, those who had higher levels of immune resilience gene expression markers at intensive care unit admission were more likely to survive,” noted Dr. co-author Justin Meunierresearch scientist at the VA Center for Individualized Medicine.
Women enjoy greater immune resilience
The researchers verified in all the populations studied that age was not the only determining factor in a person’s response to inflammatory stress. Some younger people with low immune resilience had the same signatures and degrees of immune health typically seen in older adults. This finding suggests that the ability to restore and maintain immunocompetence at earlier ages may be related to life span.
Across populations and species, they also found that females exhibited higher levels of optimal immune resilience more frequently than males. Genetic studies in humans and evaluation of mice with a genetic basis for lower immune resilience suggest that immune resilience can be gauged by variations in genes. In particular, mice with lower immune resilience were more susceptible to severe Ebola infection.
Immune monitoring could have a major impact on public health, says Ajuja, noting that assessing degrees of immune health estimated by CD8+ and CD4+ counts is a simple way to monitor immune resilience. These assessments are useful in identifying people at increased risk of developing diseases that affect the immune systemhow patients respond to treatment and whether and to what extent they will recover.