*3.2. Primary Peach Allergy*

Primary food allergy to peach, in which the sensitization occurs through the ingestion of the food, is mainly related to nsLTP Pru p 3, although some studies reported primarily airborne sensitization to nsLTPs [52,53].

In the Mediterranean area, there is a high rate of sensitization to nsLTPs, which represents the most frequent cause of both primary food allergy and food-dependent anaphylaxis in adults living in these countries [54,55].

The sensitization to Pru p 3 often occurs early in life. It may be isolated (monosensitization) or associated with multiple nsLTP sensitizations, which may lead to multiple plant-food allergies (nsLTP-syndrome) [56].

Pru p 3 sensitization may be asymptomatic or manifest with variable symptom severity, ranging from OAS to anaphylaxis [57,58].

OAS and contact urticaria are the most frequent clinical patterns observed in LTP hypersensitivity. Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea) may occur as isolated symptoms or in association with the cutaneous, respiratory, or cardiovascular symptoms involved in anaphylaxis [57].

A study on LTP syndrome reported that in a group of 87 patients sensitized to Pru p 3, 44% had anaphylaxis, 43% presented OAS or urticaria, and 13% were asymptomatic. The culprit food belonged to the *Rosaceae* family in 48.8% of the subjects, and the most frequent food involved was peach in both symptomatic groups [59].

Co-sensitization to birch pollen (Bet v 1) and/or to profilin is associated with a lower prevalence of severe reactions and a higher prevalence of local reactions (OAS) [58].

A large prospective study evaluated the phenotype and severity biomarkers of peachallergic patients sensitized to Pru p 3. The authors showed that most patients were sensitized to other LTP-containing plant foods (LTP syndrome), while only 6.8% were LTPmonoallergic (reacting only to peach and not to other plant foods). Subjects with LTP syndrome had a younger onset of peach allergy, and more asthma and sensitization to Parietaria and profilin than the LTP-monoallergic patients. Anaphylaxis was significantly more frequent in the LTP-monoallergic group, which had no sensitization to profillin. The presence of profilin sensitization was associated with a lower risk of anaphylaxis. No correlation was observed between SPT diameter, Pru p 3 sIgE level, level of nsLTP sensitization, and severity of reaction to peach [60].

Individuals with sensitization to Pru p 3 may develop cross-sensitization to other nsLTPs containing plant foods due to the structural homology between different nsLTPs. Pru p 3 shows a sequence homology from 62% to 81% with analog proteins from apple (Mal d 3), apricot (Pru ar 3), plum (Pru d 3), cherry (Pru av 3), orange (Cit s 3), strawberry (Fra a 3), and grape (Vit v 1). Other LTPs with a structural homology with Pru p 3 are present in peanut (Ara h 9), wheat (Tri a 14), hazelnut (60% with Cor a 8), and walnut (66% with Jug r 3) [61,62]. The risk of cross-reactivity most frequently involves the fruits of the Rosaceae family (apple, plum, apricot, cherry), but also nuts and peanuts. The clinical pattern ranges from local oropharyngeal symptoms up to anaphylaxis [62].

Co-factors are often involved (up to 40% of cases) in clinical expression: fasting, exercise, menstruation, and NSAID could determine the appearance of symptoms in patients sensitized to nsLTPs or influence symptom severity. According to Pascal et al., a cofactor is identified as precipitating anaphylaxis in 32.4% of nsLTPs allergic patients [20].

Sensitization nsLTPs could also be involved in food-dependent exercise-induced anaphylaxis (FDEIA), provoked by the combination of food ingestion and physical exercise within 4 h of food ingestion and within one hour of the start of exercise [63].

In patients with peach-FDEIA, Pru p 3 is the most frequent sensitizer, followed by Pru p 7 [56,63,64].
