# Pollen-Food Allergy Syndrome: Allergens, Clinical Insights, Diagnostic and Therapeutic Challenges
## 4 PFAS Pathogenesis
Conversely, certain processing techniques, such as fermentation, can enhance the immunogenic properties of allergens, highlighting the importance of dietary habits in PFAS pathophysiology [72]. The gut microbiota also plays a role in modulating the immune response to food allergens. Individuals with disrupted microbial diversity or dysbiosis may exhibit heightened allergic reactions due to altered immune regulation. Short-chain fatty acids (SCFAs) produced by commensal bacteria have been shown to influence the activity of regulatory T cells (Tregs), which are essential for maintaining immune tolerance [75]. A reduction in SCFA levels could impair Treg function, exacerbating the allergic response in PFAS [76]. Lastly, individual genetic predispositions, including polymorphisms in genes encoding cytokines or immune receptors, may influence susceptibility to PFAS. Certain genetic variants may promote a stronger Th2-skewed immune response or impair mechanisms of tolerance, making affected individuals more prone to cross-reactivity [77]. Understanding these genetic and environmental interactions is crucial for developing targeted interventions and improving the management of PFAS. The intensity of the allergic reaction depends on multiple factors beyond just the molecular similarity between the inhalant and food allergens. One critical factor is the concentration of the allergen in the food, as higher levels of allergenic proteins are more likely to elicit a stronger immune response. Another important determinant is the amount  
Figure 1: The figure illustrates the PFAS mechanism, highlighting its two main phases: the sensitization phase and the clinical phase. During the sensitization phase, inhaled allergens, such as pollen, are presented by antigen-presenting cells to T helper 2 cells. These cells release cytokines like IL-4 and IL-13, which stimulate B cells to produce allergen-specific IgE antibodies. The IgE antibodies bind to the surface of mast cells, effectively priming them for future allergen exposure. During the clinical phase, ingestion of a cross-reactive allergen (e.g., fruits or vegetables) leads to the binding of the allergen to IgE on the surface of mast cells. This triggers mast cell degranulation, releasing inflammatory mediators such as histamine, leukotrienes, and prostaglandamins. These mediators cause the characteristic symptoms of PFAS, including itching, swelling, or discomfort in the oral cavity, and also systemic symptoms. The cross-reactivity between pollen allergens and structurally similar food allergens is central to the development of PFAS symptoms. of food consumed, as consuming larger quantities of a triggering food increases the overall allergen load, thereby amplifying the risk and severity of the reaction [78]. Additionally, the individual's sensitivity threshold plays a pivotal role. This threshold varies significantly between individuals and is influenced by factors such as the degree of prior sensitization, the individual's immune response, and the presence of comorbid conditions such as asthma or mast cell disorders [66]. For example, highly sensitized individuals may experience symptoms with even trace amounts of allergens, whereas others may tolerate small exposures without significant reactions [78]  
Environmental and physiological cofactors, such as alcohol, exercise, or medications, can further amplify the immune response, making the reaction more severe [79]. These cofactors influence the body's immune or physiological state in ways that enhance allergen absorption, increase immune cell activation, or lower the threshold for triggering a reaction. Alcohol, for example, is known to affect the permeability of the gastrointestinal lining, allowing allergens to cross into the bloodstream more readily [80]. It also impacts the immune system by modulating the activity of mast cells and basophils, leading to an exaggerated release of histamine and other inflammatory mediators. This heightened response can turn a mild, localized reaction into a more systemic one [60].