# Pollen-Food Allergy Syndrome: Allergens, Clinical Insights, Diagnostic and Therapeutic Challenges
## 6 Protein Families Involved in PFAS
### Thaumatin-like Proteins (TLPs)  
Thaumatin-like proteins (TLPs) are a family of pathogenesis-related (PR) proteins involved in plant defense mechanisms. TLPs are named for their structural resemblance to thaumatin, a sweet-tasting protein first isolated from miracle berry arils (_Thaumatococcus daniellii_) [165]. Their discovery as allergens in both pollens and plant-derived foods has highlighted their role in PFAS.  
TLPs are small proteins, typically ranging between 20 and 30 kDa, characterized by a conserved structure that includes 16 conserved cysteine residues forming eight disulfide bridges [166]. These disulfide bonds confer remarkable stability to heat, enzymatic digestion, and acidic conditions, allowing TLPs to retain their allergenic properties even after cooking or processing [167]. Their structural resilience, combined with their ability to bind sugars and other small molecules, makes them effective in defending plants against pathogens, such as fungi and bacteria. TLPs are often classified as PR-5 proteins [168] and play a critical role in protecting plants during stress conditions like infection, drought, or cold [169].  
In allergology, TLPs have been identified as significant contributors to sensitization, particularly through exposure to certain pollens. Among these, the Cupressaceae tree family, including species like Japanese cedar (Cry j 3) and cypress (Cup s 3), serves as the primary source of sensitization [170]. Sensitization to these pollen-derived TLPs can lead to cross-reactivity with homologous TLPs in foods, triggering PFAS symptoms. While cypress pollen is the most well-documented source, emerging research suggests that other pollens may also contain TLP allergens, although their clinical significance remains underexplored [117].  
The prevalence of TLP-related allergies is closely tied to geographic and environmental factors. In regions like Japan and the Mediterranean basin, where Cupressaceae trees are abundant, sensitization to pollen-derived TLPs is more common [171]. The prevalence of food allergies related to TLPs is less well-documented but is likely higher in areas where dietary staples include TLP-rich foods like apples, peaches, and tomatoes. In Northern Europe and North America, where PR-10 proteins dominate allergen profiles, TLPs are less frequently implicated in allergic diseases [172]. However, their global prevalence may be underestimated due to the limited availability of diagnostic tools specifically targeting TLPs [117].  
Notable examples in fruits include Mal d 2 in apples, Pru av 2 in sweet cherries, Pru p 2 in peaches, Act d 2 in kiwi, and Mus a 4 in banana. In vegetables, TLP allergens such as Sola 1 2 in tomatoes, Cap a 1 in pepper, and Api g TLP in celery have been reported [117].  
Clinically, TLP allergy manifests as OAS, where affected individuals experience itching, tingling, or mild swelling of the lips, mouth, and throat after consuming TLP-containing foods like certain fruits (e.g., apples, kiwis, or peaches) or nuts [169]. More severe reactions, though less common, include urticaria, gastrointestinal symptoms (nausea, abdominal pain, or diarrhea), and respiratory distress. In rare cases, anaphylaxis may occur, especially in sensitized individuals with high exposure [173; 174]. Symptoms are often seasonal, coinciding with the pollination periods of tree or grass species that express TLP, and are exacerbated by co-factors like exercise or alcohol consumption [171].