Are pollen cysteine proteases allergenic?

Respiratory allergy affects over 500 million people globally, posing a significant public health challenge. Grass pollen (GP) is a notable contributor to allergic respiratory disease, including allergic rhinitis (AR), seasonal allergic asthma, and in particular, large-scale thunderstorm asthma (TA) events. The complex interactions between innate and adaptive immune pathways that induce allergic sensitisation to pollen that remain poorly understood. Cysteine proteases (CPs) are enzymes found in a range of aeroallergen sources, including faecal material of house dust mite (HDM) and pollen. These enzymes can disrupt epithelial barrier integrity and, as such, are contributors to HDM, and potentially GP allergenicity. However, previous research has mostly focused on HDM-derived CPs. Here we apply a narrative review method and bioinformatic analysis to compare the allergenic properties of CPs from GP and HDM, and to consider how pollen-derived CP might contribute to the induction of allergic sensitisation. The primary findings indicate that identified pollen-derived CP allergens of Ragweeds ( Ambrosia genus; Amb a 11; Amb t CP) and Bermuda grass ( Cynodon dactylon ; Cyn d CP) arise from distinct biochemical CP protein subfamilies encoded by separate gene loci. Specific IgE reactivity with Amb t CP and Cyn d CP is yet to be verified in other relevant patient populations or by the International Union of Immunological Studies (IUIS) Allergen Nomenclature Committee. The allergenicity of pollen-derived CP is likely augmented by modifying environmental factors such as climate and by microbiomes associated with pollen. Knowledge of pollen allergen-airway epithelial interactions is essential to understanding mechanisms by which GP initiate and exacerbate airway inflammation. However, there is currently limited evidence supporting CPs as allergens within GP, and few mechanistic studies explore the role of pollen CP in driving allergic inflammatory processes.