# Pollen-Food Allergy Syndrome: Allergens, Clinical Insights, Diagnostic and Therapeutic Challenges
## 6 Protein Families Involved in PFAS
### Lipid Transfer Proteins (LTPs)  
LTPs are a family of small (9-10 kDa), highly stable proteins, part of the prolamin superfamily, and involved in plant defense and lipid transport. This stability arises from four conserved disulfide bridges that create a rigid tertiary structure, making LTPs resistant to heat, enzymatic digestion, and acidic conditions. Unlike other panallergens such as PR-10 proteins or profilins, this stability allows LTPs to retain their allergenic properties even after cooking or digestion, significantly increasing their potential to cause severe allergic reactions. LTPs bind and transport lipids between membranes, playing an essential role in plant cell metabolism and protection against environmental stressors such as drought, pathogens, and UV radiation. Pollens such as Ole e 7 from olive trees, Pla a 3 from plane trees, Art v 3 from mugwort, and Par j 1 from pellitory-of-the-wall are well-documented sources of LTP sensitization. Among fruits, peach (Pru p 3) stands out as the most significant allergen, often serving as the prototype for LTP-mediated allergic reactions [141]. Similarly, apple (Mal d 3) and cherry (Pru av 3) are common triggers, along with apricot (Pru ar 3) and plum (Pru d 3). In the category of vegetables, tomato (Sola 1 3) and celery (Api g 2) are frequently implicated, particularly in regions where these foods are staples. Nuts are another major source of LTP allergens, with hazelnut (Cor a 8) and walnut (Jug r 3) often associated with systemic reactions due to their heat-stable properties [142]. Peanut (Ara h 9) also contributes significantly to LTP-related allergies (LTP syndrome), particularly in individuals who experience severe reactions [100; 141; 143]. There have also been cases of PFAS to pistachios due to cross-reactivity with LTPs from pellitory-of-the-wall, particularly in the Mediterranean region [144; 145]. The prevalence of LTP sensitization and its clinical significance vary by geographic region. In Mediterranean countries, LTPs are the most significant cause of food allergies and PFAS, with a high prevalence (up to 30%) of sensitization to Pru p 3, the peach LTP that serves as the archetype of this allergen family [143; 146; 54]. In contrast, LTP-related allergies are less common in Northern and Central Europe, where PR-10 proteins (e.g., Bet v 1) and profilins dominate the allergenic landscape [100]. This regional variation reflects differences in dietary habits, pollen exposure, and environmental factors. In Mediterranean regions, the high consumption of LTP-rich foods such as peaches, nuts, and apricots [148; 149], coupled with frequent exposure to olive and plane tree pollen [150; 151], increases the likelihood of sensitization. In non-Mediterranean regions the primary LTP sensitiizer may not be Pru p 3, but other pollens, such as mugwort [142] or cannabis [152]. LTP-mediated PFAS often presents with more severe symptoms compared to other allergenic families such as PR-10 proteins or profilins. Due to their heat and digestion stability, LTPs can trigger systemic reactions, including anaphylaxis, even after ingestion of cooked or processed foods [141]. LTPs are also unique among panallergens in their potential to elicit allergic reactions to wheat and other cereals, especially in the context of exercise. Unlike other allergen families, LTPs, such as Tri a 14 in wheat, are implicated not only in PFAS but also in wheat-dependent exercise-induced anaphylaxis (WDEIA) [153]. In these cases, ingestion of wheat followed by physical activity amplifies the immune response, leading to severe systemic reactions, including anaphylaxis. Furthermore, Tri a 14 plays a distinct role in baker's asthma, an occupational allergy caused by inhaling wheat flour allergens. Unlike many other LTP-related allergies, baker's asthma does not require prior sensitization to pollens containing LTPs, as sensitization occurs directly through inhalation of wheat flour particles [154].