LUMC researchers: high levels of lipids in blood protect against allergies

3 February 2023
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People with relatively high levels of lipids in their blood are less likely to develop allergic conditions such as eczema and asthma. These lipids cause genes that play a key role in allergic reactions to be less active. The results of this study in the Leiden University Medical Center (LUMC) are published in Nature Communications.

Bas Heijmans and Koen Dekkers calling from Sweden

"We already knew that lipids in our blood, such as triglycerides and cholesterol, can influence the behaviour of immune cells," says Professor of Biomedical Data Sciences Bas Heijmans. "We now show that these lipids dampen the activity of genes that play a key role in allergies." As a result, allergic reactions are less likely to occur.

First, the researchers mapped which genes are active in immune cells in over 3,200 people. "This turned out to be more than 17,000 genes," says Koen Dekkers, first author of the study. "Then, step by step, we figured out exactly which genes are affected by lipids in the blood, leading us to a group of genes that trigger allergic reactions." Using a cutting-edge analysis method in which the researchers combined blood levels of lipids, activity of genes and known genetic differences between people, they were able to show that this correlation is actually causal.

What happens in allergy?

An allergic reaction is characterised by an exaggerated response of your immune system to a harmless substance, think of pollen leading to hay fever. The researchers found that lipids mainly affect genes active in basophils. These are immune cells that, among other things, produce histamine and are crucial in triggering an allergic reaction.

Saturated vs unsaturated

Triglycerides in particular have an effect on these basophils, the researchers discovered. Blood triglyceride levels are determined partly by our DNA, but mainly by diet. "And that, of course, is very interesting," says Heijmans. "This could mean that patients with severe allergic reactions might benefit from administering extra triglycerides, or more precisely, the fatty acids that make up triglycerides." However, we are not there yet, Heijmans stresses. "First we need to test whether and, if so, which fatty acids actually have these beneficial effects. Is it mainly the healthy, unsaturated fatty acids? That would be good news. Or perhaps the unhealthy, saturated fatty acids?" It is also not clear yet how lipids change the behaviour of immune cells in this direction.

Unexpected twist

Allergies were not exactly Heijmans and Dekkers' area of expertise. "We did not expect at all that this study would point us in that direction," says Dekkers. Their eyes were set on cardiovascular diseases, in collaboration with Professor of Cardiology Wouter Jukema. "These diseases are driven by the interaction between fats and the immune system," says Heijmans. "We expected to discover in what way lipids affect genes involved in cardiovascular disease. But the effect on allergic reactions was much stronger." Their research had an unexpected outcome, but that doesn't dampen their enthusiasm. Heijmans: "Such a surprising discovery is like icing on the cake for a scientist."

Will allergies now become a new focus area within their research? Dekkers, who now works at Uppsala University in Sweden, does not rule it out for the longer term: "I definitely see follow-up research in it, and it could just be that I pick this up again later." Heijmans: "Wouter Jukema and I are as interested as ever in the effect of fats on immune cells, but are now focusing again on their role in cardiovascular disease."

This study is a result of the national atherosclerosis consortium Genius, funded by the Heart Foundation and the Dutch CardioVascular Alliance. The research data used in this study were brought together thanks to a collaboration between the Vrije Universiteit and the university medical centres of Rotterdam, Groningen, Maastricht, Utrecht and Leiden within BBMRI-NL.