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Could a Novel Immunotherapy Approach Help Combat Cat Allergy?

CAT allergies are among the most common allergies, affecting between 10 and 20% of the global population. Symptoms range from mild-to-moderate conditions, such as allergic dermatitis, nasal congestion, and postnasal drip, to the development of chronic asthma. Fortunately, researchers from the Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg, have discovered a novel immunotherapy strategy for managing cat allergy.

Although various drug-based treatments exist to alleviate symptoms, these are often ineffective and fail to address the underlying condition itself. Allergy-specific immunotherapy (AIT) has therefore become an increasingly valuable therapeutic tool to ensure longer lasting control in patients with more advanced clinical manifestations. AIT involves subcutaneous administration of gradually increasing quantities of the relevant allergen molecule until a critical dose is reached that induces immunologic tolerance. Cat AIT is based on the injection of the Fel d 1 glycoprotein, the most important allergen in disease pathogenesis. When discussing the rationale for the research, Dr Cathy Leonard, co-corresponding first author, commented: “We sought to explore new means of increasing the anti-inflammatory activity of AIT with the known immunomodulatory adjuvant CpG, but at a higher dose than previously used.”

To mimic the conditions of human immunotherapy trials, 8-week-old female BALB/c mice underwent AIT with high-dose CpG in combination with endotoxin-free Fel d 1. AIT-specific immune signatures were then assessed using a range of multidimensional immune phenotyping techniques, including mass cytometry (CyTOF). AIT with Fel d 1/CpG was found to improve all hallmarks of allergy, significantly improving lung resistance as well as reducing airway eosinophilia relative to untreated control mice. Additionally, increased secretion of the TNFα cytokine was recorded in the bronchoalveolar lavage fluid of AIT-treated mice. High-dimensional CyTOF analysis detected a corresponding elevation in TNF receptor 2 (TNFR2) expression, which was localised to plasmacytoid dendritic cells, natural killer cells, and regulatory T and B cells in the tissues of AIT-treated mice. These final two observations highlight the key involvement of the anti-inflammatory TNF/TNFR2 signalling cascade in promoting allergy regulation and tolerance.

When discussing the relevance of the research findings, Prof Markus Ollert, senior lead author of the study, noted: “Based on our data, we believe that CpG deserves reconsideration as an effective AIT adjuvant in humans and that our work sets the bases for the development of novel successful immunotherapeutic treatments for allergies.”