Ignacio Jesús Dávila González
Head of the Allergy Service at the University Hospital of Salamanca, Professor at the Faculty of Medicine of the University of Salamanca and President of the Spanish Society of Allergology and Clinical Immunology
The studies seem to me to be of very good quality, very well thought out and developed.
The main issue is that the memory of the immune system for the production of immunoglobulin E (IgE) is not well understood and has focused on plasma cells, many of which are short-lived; however, the production of specific IgE directed against an allergen can be maintained for prolonged periods of time, once sensitisation has occurred. These two studies describe a population of type 2 memory B cells, which express IgG, but also the low-affinity receptor for IgE, FcεRII or CD23, the IL-4 receptor and the IgE heavy chain gene.
Two aspects are important:
- These cells appear to be able to contribute to the production of specific IgE (e.g. against Ara h 2 [the major peanut allergen] in the case of the first study) by differentiating into plasma cells, which could explain the maintenance of very high levels of specific IgE against Ara h 2 in some patients.
- It appears that administration of sublingual immunotherapy may lead to an increase in this cell type as early as one month after treatment, which may also switch to the production of allergen-specific IgG1 or IgG4. The latter is well known to increase with allergen immunotherapy.
Finally, these type 2 memory B cells express the alpha chain of the IL4 receptor and the alpha 1 chain of the IL13 receptor. Blocking these receptors could be an interesting treatment for the induction of tolerance to allergens. Indeed, dupilumab, a monoclonal antibody targeting the IL4 receptor alpha chain and blocking IL4 and IL3 signalling transmission has been shown to reduce total IgE and specific IgE levels and could lead to the development of tolerance.
In terms of limitations, these are initial data that require further confirmation.