Allergic response to house dust mites is age-dependent
In adults with a house dust mite allergy, a cascade of inflammatory
signals on the surface of the airways leads to airway remodeling. This
process cannot be influenced by standard cortisone therapy. Researchers
at Helmholtz Zentrum München and the Technical University of Munich have
reported these findings in the latest issue of the Journal of Allergy
and Clinical Immunology.
Worldwide more than 300 million people suffer from asthma. A common
symptom in this context is airway remodeling: a pathological remodelling
of the airway structure due to misdirected repair processes. Depending
on the age of the patient, messenger substances called leukotrienes play
an important role here, as researchers led by Dr. Julia Esser-von Bieren
have now discovered. "Although drugs that target the leukotriene cascade
exist, we still know too little about the exact disease mechanisms,"
said the group leader at the Center for Allergy and Environment (ZAUM),
a joint research center of Helmholtz Zentrum München and the Technical
University of Munich.
 In the current study, the researchers were particularly interested in
whether there were age-dependent differences in the expression of an
allergy to dust mites. In collaboration with Professor Benjamin Marsland
of the University Hospital CHUV in Lausanne, they studied a
corresponding experimental model. It was found that an extract from
house dust mites elicited different responses, depending on the time
window in which it came in contact with the immune system.
"It is striking that leukotrienes appear to play an important role,
especially when adults acquire an allergy," said Katharina Dietz, lead
author of the study. "They are part of a whole cascade of signals
ultimately leading to a response to the house dust mite extract."
According to the study, in particular the signaling protein Wnt5a, the
enzymes transglutaminase 2 and phospholipase A2 as well as the
leukotrienes themselves are involved. The scientists were able to
confirm these results in human cells and in tissue from nasal polyps of
patients.
Cortisone cannot halt progression
It was also interesting for the researchers to find out where these
molecules come from. They showed that especially the epithelial cells of
the bronchi are the drivers of the cascade. "Previously it was assumed
that in allergies, leukotrienes are mainly produced by certain white
blood cells, the eosinophil granulocytes," said study leader Esser-von
Bieren.
However, the results are not only relevant for understanding the
disease, but also for the therapy. "This cascade cannot be stopped
through treatment with cortisone, the standard treatment for allergy,"
said Esser-von Bieren. She therefore considers it possible that the
results could also impact allergy therapy: "The strong presence of the
leukotriene cascade in the inflamed airway epithelium refutes the common
assumption that structural cells can be neglected as leukotriene
producers. On the contrary: In a chronic, cortisone-resistant
inflammation in the form of asthma or nasal polyps, the use of drugs
targeting the epithelial leukotriene cascade should be considered,
depending on the age and allergy status of the patients."
This includes e.g. the increased deposition of connective tissue in
the wall of the bronchi, an increase of mucus-producing gland cells in
the bronchial epithelium or increased growth of muscle cells in the
airway walls. An important trigger for this misdirected remodeling is
the apparent ongoing inflammation in the airways.
- MNT
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