French scientists have found that when the lungs are exposed to an allergen (pollen, spores, dust mites, etc.), an ‘alarmin’ called TL1A is released as the body and immune system attempts to defend itself, leading to inflammatory reactions.
This discovery could lead to a new treatment to block these alarmins and greatly reduce the symptoms of severe asthma attacks, although it will likely take years to develop.
Allergies are the fourth most common illness in the world according to the World Health Organisation, with 17 million people affected in France.
Some four million people in France are asthmatic, with 5-10% of these suffering severe asthma. There are several hundreds of deaths every year from severe asthma attacks.
Respiratory allergic inflammations
The study was performed by scientists at CNRS, Inserm and the Université Toulouse III – Paul Sabatier. It is the third alarmin found to be present at the start of respiratory allergic inflammations.
The scientists were researching the cause of inflammatory allergic reactions in the lungs and the effects of airborne allergens such as mould and pollen.
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They became particularly interested in Alternaria alternata, the only mushroom spores linked to severe asthma attacks.
When the spores are released, they can provoke what is called ‘epidemic’ or ‘thunderstorm’ asthma. Hospitals often see an influx of patients suffering severe attacks after a storm.
Some 15 minutes after exposure to Alternaria alternata, the epithelium lung cells (the cells which line the lungs) release molecules named ‘alarmins’.
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“Human bodies continuously produce these alarmins,” said Jean-Philippe Girard, director of research at Inserm and co-director of the study.
They are like alarm bells for the immune system, warning it that it is under attack.
“The alarmins are released because allergens have been detected. This launches a cascade of immune responses.”
This is the third lung alarmin to be discovered. Mr Girard and his team identified IL-33 in 2003 in Toulouse, while the second was discovered by American researchers. There may be one or two more alarmins, but it is very unlikely that there are more than that, so the discovery is important.
Treatment could take years to develop
The study found that TL1A and IL-33 work in conjunction with one another and over-activate white blood cells, leading to a bigger inflammation, said Mr Girard.
Jean-Philippe GirardJean-Philippe Girard
Alarmins are not just involved in allergic reactions but can also be released during illnesses such as chronic obstructive pulmonary disease (COPD, common in smokers) or non-allergic asthma.
A form of treatment currently being tested is based on antibodies that block IL-33 alarmins as soon as they are released, preventing them from alerting the white blood cells. The results of this research will be released in 2025.
A similar treatment for TL1A could be developed in five to 10 years, although it is only likely to help people with severe respiratory allergies as one injection could cost €1,000.
The TL1A molecule is also produced in the intestine in cases of Crohn’s disease, playing a similar role in causing inflammation.
The presence of TL1A is not surprising in of itself. However, it was thought it would appear at the bottom of the “pyramid of reactions,” as Dr Girard puts it, not the top. This means it is the cause of some symptoms, rather than a consequence of them.
Respiratory illnesses such as COPD and asthma are the third largest cause of death in the world.
“Anti-alarmin treatment could be a revolution for sufferers, particularly in cases of severe COPD, where patients do not really have treatment available at the moment,” said Dr Girard.
