# Pollen-Food Allergy Syndrome: Allergens, Clinical Insights, Diagnostic and Therapeutic Challenges
## 6 Protein Families Involved in PFAS
### Gibberellin-Regulated Proteins (GRPs)  
Gibberellin-Regulated Proteins (GRPs) are an emerging family of plant allergens that play a role in PFAS. These proteins are regulated by gibberellins, a class of plant hormones involved in growth and development [155]. While GRPs were initially studied for their role in plant physiology, their identification as allergens in both pollens and foods has highlighted their clinical significance in allergic diseases [118; 156].  
GRPs are small proteins (7-8 kDa) with a high degree of stability, owing to their conserved cysteine residues that form multiple disulfide bridges [118]. This structural feature makes them resistant to heat and enzymatic digestion, enabling them to retain their allergenic potential even after cooking or processing. Their primary function in plants includes regulating cell wall modifications, responding to stress conditions, and facilitating growth processes mediated by gibberellins [155]. These properties are crucial for plant survival and adaptation to environmental changes but also contribute to their allergenicity in humans.  
In the context of allergies, GRPs have been identified as significant sensitizers in certain pollens. The most notable example is BP14 (cypmaclein, Cup s 7), a GRP found in cypress pollen (_Cupressus semperviens_), which is highly allergenic in regions where cypress trees are abundant, such as the Mediterranean basin [157]. Sensitization to Cup s 7 has been shown to cross-react with GRPs in foods, such as Pru p 7 in peaches and similar GRPs in oranges and other fruits [158]. This cross-reactivity forms the basis of the \" cypress-peach syndrome\", where individuals sensitized to cypress pollen experience allergic reactions after consuming peaches [159; 160; 161].  
The prevalence of GRP-related allergies is closely linked to environmental and dietary factors. In the Mediterranean region, where cypress trees are widespread and fruits such as peaches and oranges are dietary staples, GRP sensitization is relatively common [162]. In contrast, GRP-related allergies are less frequently reported in Northern and Central Europe, where exposure to cypress pollen is lower, and other allergenic families, such as PR-10 proteins and profilins, dominate. A study from Japan observed that 65% of patients allergic to fruits were sensitized to GRPs [158]. The geographic variability of GRP sensitization reflects the regional distribution of cypress trees and the consumption patterns of GRP-containing foods.  
In addition to peaches (Pru p 7) and Japanese apricots (Pru m 7), GRP allergens have been identified in a wide range of fruits, vegetables, and pollens. Notable examples include sweet cherry (Pru av 7), orange (Cit s 7), pomegranate (Pun g 7), and bell pepper (Cap a 7). Further GRPs have been described in raspberries (Rub i 7), kiwi (Act d 7), apples (Mal d 7), tomatoes (Lyc e 7), melons (Cuc m 7), and strawberries (Fra a 7). In pollens, GRP allergens seem to be confined to the Cupressaceae tree family, with key examples being Cup s 7 (cypress), Cry j 7 (Japanese cedar), and Jun a 7 (juniper) [118; 163; 158].  
Clinical symptoms of GRP-related allergies range from mild to severe and can affect multiple organ systems. Localized symptoms, such as oral itching, tingling, and swelling, often occur after consuming GRP-containing foods like peaches, oranges, or apricots [163]. While these reactions are typically mild and self-limiting, the heat and digestion stability of GRPs can lead to systemic symptoms, including gastrointestinal distress (nausea, vomiting, and abdominal pain), urtic, and, in rare cases, anaphylaxis [158; 163]. Additionally, respiratory symptoms such as allergic rhinitis and asthma may arise in individuals sensitized to GRPs in cypress pollen, particularly during the pollen season [164; 120].