Petter Brodin wants to understand your immune system
Is your immune system functioning as it should? The question is not as simple to answer as one might think. Professor Petter Brodin is trying to understand more about it. At the same time, he hopes to help patients that are severely affected with post-COVID and other conditions where the regulation of the immune system is not working.
Text by: Cecilia Odlind, first published in Medical Science No 3 2024
Being able to measure and interpret how our immune system works, especially in children, is the goal of paediatrician and professor Petter Brodin's research.
“It may sound trivial, but it is actually very difficult. For other organ systems in the body, there are functional tests. For example, there are tests to find out if your liver or kidneys are working as they should. But when it comes to the immune system, there is nothing like that,” says Petter Brodin.
Only when it comes to extremes, such as AIDS patients or patients born with severe deficiencies in their immune systems, can we recognise them, he explains.
“But there is no doctor in the world who can say if your immune system is good or bad. Today, it is not possible to predict if you, for example, have a high or low risk of developing an autoimmune disease in a few years, be affected by allergies or asthma, or a severe COVID infection,’ says Petter Brodin.
According to him, the knowledge gaps are partly due to previous research being dominated by experiments on mice.
“Our immune system is shaped by the environment we live in, more so than our genetics. That environment cannot be recreated in laboratory mice. They do not eat our food. They do not have the same bacteria. They live a completely different type of life. So, I believe we need to study humans directly to a greater extent to understand the human immune system,’ says Petter Brodin.
His research group works within what is called systems immunology, where they have developed new techniques to measure all the different components of the immune system in a blood sample.
“These factors are constantly interacting and it is difficult to interpret them if you only look at the individual components separately. We try to understand the immune system as precisely that, a system, and how the different elements interact and work together,’ says Petter Brodin.
Based on these premises, the researchers study, for example, what has gone wrong in patients whose immune systems are not functioning as they should or how children's immune systems develop during the first months of life. They have also studied the difference between men's and women's immune systems and the role of sex hormones. In a recent article published in the renowned scientific journal Nature, the group recently presented results from studies on individuals who have undergone gender-affirming treatment and been treated with testosterone.
“They experienced increased hair growth, a changed voice, and larger muscles, as expected. However, the changes in the immune system were not something the individuals noticed, at least not in the short term. But from an immunological perspective, it was revolutionary; we saw several changes that were common among all these individuals despite their initial differences,” says Petter Brodin.
Understanding gender differences
Many autoimmune diseases, such as lupus or Sjögren's disease, are much more common in women. The researchers observed that certain parts of the immune system closely linked to these diseases were suppressed by testosterone.
“It helps us to understand how hormones actually affect our immune system,” he says.
Severe COVID-19 is another example where there are gender differences, but where men are more often affected than women, just as with most infections. Petter Brodin believes that the differences in the immune system between men and women can be explained by evolutionary development.
“In women, who invest much more in reproduction than men, immunological processes that maximise their chances of reproduction have been favoured evolutionarily. In men, however, muscle growth and strength have been favoured. We believe that testosterone stimulates immunological processes that benefit this,’ he says.
Women, for example, may need to adjust their immune system during the menstrual cycle. During the fertile phase, a woman's immune system needs to be suppressed so that the uterus can allow an egg to implant without being rejected, explains Petter Brodin. Similarly, other changes occur in life that cannot be written into the genes, such as the transition from childhood to adolescence.
“We believe that hormonal regulation may be a general principle for how the immune system can change in relation to shifting conditions and needs throughout life,” says Petter Brodin.
He reiterates that these phenomena can be difficult to study in animal experiments.
“I believe that to some extent we have been misled by studying many processes in simplified model systems. For certain questions and types of studies, animal experiments can be extremely valuable. We cannot take samples from humans as we wish, especially not from small children. But the problem arises if all studies are conducted on animals. There is a risk of getting lost and forgetting that there are biological differences between mice and humans,” says Petter Brodin.
The role of bacterial flora
He and his colleagues are also trying to understand how the bacterial flora that colonises us early in life is related to the risk of certain immunological diseases, such as the effect of antibiotics early in life, breastfeeding or infections.
When the pandemic arrived, it was natural for Petter Brodin to redirect his research to focus heavily on COVID-19.
“We have such good methods for studying the immune system, so I thought it was important to contribute. We were the first in the world to report on what happens in the immune system during a hyperinflammatory condition, which in rare cases can affect children two to four months after a SARS-COV-2 infection. The condition, known as MIS-C, can be life-threatening. Several hundred children were affected in Sweden,” explains Petter Brodin.
He found it difficult to understand why such severe symptoms appeared so long after the initial infection and began reading more about adult patients with long-term symptoms. Could there be a common denominator between these different conditions that arise after a SARS-CoV-2 infection? This became Petter Brodin's entry point into post-COVID studies. The research has since resulted in a theory that the virus remains in certain tissues in some individuals.
“For some reason, the virus is not eliminated. Why this is the case and how to treat the condition is what we are trying to understand right now,” he says.
Can antiviral medicine help?
The research group is conducting a clinical trial together with researcher Judith Bruchfeldt’s multidisciplinary team, in collaboration with the pharmaceutical company Pfizer, where they are investigating whether antiviral medication for 15 days can remove viral reservoirs in tissues. The patients participating in the study are severely ill with obvious organ damage many months after a mild to moderately severe SARS-CoV-2 infection.
“We wanted to focus on the sickest group to avoid the questioning of post-COVID as a psychosomatic illness that is more in the mind than in the body,” he says.
The most severe cases also have the greatest needs, he believes.
“Their lives are ruined. These are individuals who perhaps were elite athletes and now, for several years, have not been able to climb a flight of stairs,” says Petter Brodin.
If the antiviral medication does not help, they want to proceed and test other strategies.
“Some might be helped by stimulating the immune system, while others have more of an autoimmune profile and need to suppress one of the hundreds of different signalling pathways that control the immune system. We really hope to be able to contribute to helping these patients,” he says.
Likes working with children
Petter Brodin is also a specialist in pediatrics. When he has been away from the clinic for a long time, he misses having the contact with his patients that he has there.
"The exciting thing about working with children is that, in addition to understanding the disease itself, what causes it and how to treat it, you must always consider the child's developmental stage. It adds another dimension to the biology, making the work with children intellectually stimulating. I have never regretted my choice of clinical specialty,” he says.
However, he misses having time for reflection in healthcare.
"Working in the Swedish health care system today is like working in a factory with an assembly line. What is counted and rewarded is how many patients you see per hour. In that environment, there is no room for a scientific mindset. It is incredibly comforting to have research to ‘escape into’,” says Petter Brodin.
About Petter Brodin
Name: Petter Brodin.
Title: Paediatrician at Karolinska University Hospital and Professor at the Department of Women's and Children's Health, Karolinska Institutet.
Age: 42.
Family: Wife, three children (7, 13 and 18 years old).
How I relax: With music! I wanted to work with music when I was young, have my own record label, radio programme and be a DJ. When I was in upper secondary school, I worked in a record shop and ran a club at Nalen in Stockholm with some friends.
Inspired by: Many, but right now I am reading the book ‘Genius’ by James Gleick, a biography of the late American physicist Richard Feynman. There is much to be inspired by in Feynman, not least his thoughts on real learning and true knowledge. This does not necessarily correlate with higher education or degrees and is unfortunately quite rare today, despite us all having better access to information than ever before.
Best research skill: I am good at engaging and getting members of my research group to work together to solve really complicated problems.
Petter Brodin about...
...to solve problems together: In our research group, we often work together rather than individually. This allows us to study more complex problems and learn from each other, making it both more enjoyable and more effective.
... irrelevant research: A colleague described top researchers as people who “do pirouettes in the corner”. They publish in prestigious scientific journals to show that they can. The goal should be to achieve new knowledge that can improve treatment and diagnostics for patients.
...‘Man cold’: The fact that men seem to be more troubled by a cold than women can probably be explained both by gender differences in the immune system and by gender differences in how much individuals focus on the discomfort.
... lack of time in healthcare: Being a doctor today is like working on an assembly line. What is rewarded is how many patients you see per hour. In that environment, the scientific mindset has no place. It is nice to be able to “escape” into research.