Cat allergy is a rapidly increasing phenomenon characterized by hypersensitivity and excessive immune response certain allergens associated with felines, in particular Fel d 1, a protein present in their saliva, on their skin and on their hair. The manifestations of this allergy can go as far as the development of serious conditions such as rhinitis and asthma, with potentially fatal outcomes. Only specific immunotherapy or desensitization can ensure effective and lasting treatment in the most severe cases: repeated amounts of allergen are administered to induce clinical tolerance and immunological vis-à-vis this allergen.
Concretely, this process generally consists of the subcutaneous injection of increasing amounts of the allergen in question, until a useful dose is reached which induces immune tolerance long-term. However, specific immunotherapy targeting cat allergy still requires some improvements, particularly in terms of efficacy and safety. Researchers at the Luxembourg Institute of Health hypothesized that more effective immunotherapy could be obtained by optimizing the immune response to induce antibody production against Fel d 1 while minimizing inflammation, thereby increasing immune tolerance to this allergen.
The body better protected from inflammation
In their study published in the journal “Allergy”, official journal of the European Academy of Allergy and Clinical Immunology, they proposed a new therapeutic approach based on the modulation of the immune system by the injection of Fel d 1, in combination with high doses of CpG oligonucleotide, an adjuvant substance. “We wanted to explore new ways to increase anti-inflammatory activity with the adjuvant CpG at a safe dose, but higher than those previously used. for this type of therapy. », Explains Dr Cathy Léonard, of the Allergy and Clinical Immunology research group at LIH and first author of the publication.
The scientists therefore proceeded by injecting allergic mice with the allergen Fel d 1 in combination with a high dose of CpG adjuvant to study the effects of this immunotherapy on alleviating symptoms of cat allergy. They observed that, compared to the allergic mice that did not receive the treatment, the allergic mice treated had significantly reduced signs of inflammation and airway hyperresponsiveness, lower levels. pro-allergic molecules (called cytokines) and IgE antibodies commonly associated with allergic responses, as well as higher levels of protective IgA and IgG antibodies.
The researchers also noticed that soon after the injection, an increase in number of immune cells involved in regulation and tolerance, namely plasmacytoid dendritic cells (pDC), Natural Killer cells, regulatory T cells (T-regs) and regulatory B cells (B-regs). These cells express higher levels of specific molecules and associated receptors, allowing them to suppress the allergen-related immune response and act as a brake. on the immune system. These results prove the powerful anti-inflammatory and antiallergic effect of their approach, with a high and safe dose of CpG adjuvant.
“We offer a preclinical model allergen-specific immunotherapy (AIT) for cat allergy, mimicking the conditions required for human clinical trials and already being optimized for future use in translational studies. Our study presents several novelties, including the use of a safe variant of the allergen Fel d 1, which is mandatory in clinical settings to avoid collateral inflammatory reactions. We show that the use of the maximum dose of CpG tolerated in humans, in combination with Fel d 1, has the ability to modulate the allergic response, with a very favorable security profile. “, Note the researchers.
Based on their data, they conclude that CpG deserves to be reconsidered as an effective adjuvant for allergen-specific immunotherapy in humans in general and that their discovery lays the foundations for the development of new effective immunotherapeutic treatments against allergies. Allergies can have skin (urticaria, dermatitis), respiratory (rhinitis, asthma) or generalized (anaphylaxis) manifestations and their prevalence has increased considerably over the past 20-30 years in industrialized countries. Inserm now estimates than 25 to 30% of the population is affected by an allergic disease.