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Food allergies can be broadly divided into primary (also defined as class A) or secondary (class B), the latter being the consequence of primary sensitization to an airborne allergen and including the pollen-food syndromes (PFS). PFS represent the most common form of food allergy in adults living in temperate climates [1], although they may be prevalent also during adolescence [2]. They encompass a broad spectrum of IgE-mediated reactions arising after primary sensitization to pollen and driven by cross-reactivity between homologous pollen and plant-derived food allergens. PFS are increasingly recognized worldwide, reflecting the combined effects of environmental exposure, climate change, and evolving dietary habits. Clinical manifestations range from mild oral allergy syndrome (OAS) to systemic reactions, including urticaria, angioedema, and anaphylaxis, depending on the biochemical stability and biophysical properties of the eliciting allergen. At a molecular level, PFS are associated with several protein families, most notably PR-10 proteins, profilins, and gibberellin-regulated proteins (GRPs). Additional allergen families, such as non-specific lipid transfer proteins (nsLTP) [3], cyclophilins, defensins, PR-1 proteins, and thaumatin-like proteins (TLPs), have also been implicated. A precise definition of the individual sensitization profile is therefore essential for accurate diagnosis, appropriate risk stratification, and the development of personalized avoidance strategies. The diagnostic work-up invariably begins with a detailed clinical history, documenting both respiratory symptoms (rhinitis, conjunctivitis and/or asthma, which may be seasonal, multiphasic, or perennial) and plant food–induced reactions, including OAS, gastrointestinal symptoms, urticaria, angioedema, anaphylaxis, or hypotension. Whenever possible, clinical history should be supported by medical documentation or patient-provided photographs. Patients frequently report reactions to multiple, botanically unrelated plant foods, reflecting the intrinsic cross-reactive nature of PFS. Asking whether the patients reacts only to raw or to both raw and cooked foodstuff is extremely important. Although double-blind, placebo-controlled food challenges remain the diagnostic gold standard, they are rarely feasible in routine practice due to logistical constraints, variability in allergen content, and the marked lability of several plant food allergens, which may degrade during blinding procedures. The second diagnostic step includes skin prick testing (SPT) and/or in vitro specific IgE assays (sIgE) using commercial extracts of airborne allergens representative of the major regional pollen sources and recombinant allergens, complemented by SPT/sIgE of plant-derived foods. However, since standard food extracts may occasionally yield false-negative results because of the heat- and pepsin-lability of several PFS-related allergens, SPT with fresh foods using the prick-to-prick technique is recommended due to its higher sensitivity. Optimal interpretation of this method requires awareness of the allergen's localization within the food matrix—e.g., nsLTPs are mainly concentrated in the peel, while PR-10 proteins and GRPs are present both in peel and pulp. Importantly, a positive test indicates sensitization but does not necessarily mean clinically relevant food allergy. When patients are monosensitized to a pollen species classically associated with PFS (e.g., birch, mugwort, or cypress) and report reactions to the corresponding plant foods, diagnosis is usually straightforward. Diagnostic complexity increases substantially in polysensitized individuals. In this case, molecular allergology (MA) allows a detailed characterization of the molecular sensitization patterns, enabling clinicians to estimate the likelihood and potential severity of food reactions, assess the risk of systemic involvement, and optimize patient management. This includes decisions regarding the prescription of emergency medications such as auto-injectable adrenaline, whose indication remains highly context- and geography-dependent and is generally restricted to selected molecular profiles, including nsLTPs, GRPs [4], and defensins expanded IgE repertoire. MA also supports rational dietary counseling, aiming to minimize unnecessary food avoidance, and helps to identify patients at risk of symptom exacerbation in the presence of co-factors [5, 6]. The algorithm is summarized in Figure 1. The main characteristics of the allergen families involved in PFS are summarized and analyzed in Table 1 and in the Supporting Information. A pollen source is not established in Mediterranean countries. Artemisia vulgaris is reported only in China. Artemisia vulgaris (only in China) Peach and other Rosaceae, Tree nuts, Cereals, Grapes, etc. Plant panallergen Peach, Apricot, Sweet Cherry Citrus fruits, Pomegranate, Bell pepper, Grapes Once the diagnosis is established, management depends largely on the biochemical properties of the culprit allergen. If the triggering protein is thermolabile, the food may often be tolerated after adequate heat treatment; conversely, foods containing thermostable allergens should be avoided both raw and cooked. Whether allergen immunotherapy (AIT) can secondarily reduce food-related symptoms in PFS remains a matter of debate. The 2015 EAACI position paper does not recommend AIT for the treatment of PFS [7]. Nonetheless, some (albeit not all) older studies investigating PR-10 proteins and profilins suggested that birch pollen subcutaneous immunotherapy may improve apple-induced OAS while data on sublingual AIT were inconsistent. More recently, it was shown that oral immunotherapy with raw apples or rMal d1 is able to reduce symptoms in PR-10 related PFS [8-10]. For profilin, older limited case reports indicate that injection AIT with non-birch pollens may reduce reactivity to foods not typically involved in PR-10-associated PFS, such as cucumber and melon. All authors contributed equally to this manuscript (coordination, writing, draft) and approved its final version. The authors have nothing to report. The authors declare no conflicts of interest. The authors have nothing to report. Data S1: all70286-sup-0001-Supinfo.docx. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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