# Pollen-Food Allergy Syndrome: Allergens, Clinical Insights, Diagnostic and Therapeutic Challenges
## 7 PFAS Diagnosis
### Exploratory Approaches in Food Allergy Testing
#### 7.5.2. Allergen-Specific IgG4 and IgA  
Elevated levels of IgG4 and IgA have been increasingly recognized as markers associated with immunological tolerance and the efficacy of oral immunotherapy (OIT) in managing food allergies. IgG4, a unique subclass of IgG, plays a pivotal role in immune reg \begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline
**Category** & **Details** & **Additional Insights** \\ \hline
**Advantages of OFC** & & \\ \hline \multirow{2}{*}{_High diagnostic accuracy_} & OFC directly confirms the clinical relevance of sensitization detected through other diagnostic tests, making it the gold standard for PFAS. & Particularly valuable when SPT or specific IgE results are inconclusive. \\ \hline \multirow{4}{*}{_Personalized management_} & Results guide tailored dietary recommendations, allowing patients to safely consume tolerable foods while avoiding problematic ones. & Reduces patient anxiety by clarifying which foods are safe in raw or cooked forms. \\ \hline \multirow{2}{*}{_Minimizing dietary restrictions_} & OFC helps prevent unnecessary avoidance of foods, improving nutrition and quality of life. & Expands dietary options and supports balanced nutrition, especially in children and individuals with multiple food restrictions. \\ \hline \multirow{2}{*}{_Clarity in complex cases_} & In polysensitized patients, OFC identifies specific triggers among cross-reactive allergens. & Essential for differentiating between cross-reactivity and primary food allergies. \\ \hline \multirow{2}{*}{_Limitations of OFC_} & OFC requires trained personnel, controlled environments, and significant time, making it less accessible in routine practice. & Requires specialized facilities, which may not be available in all healthcare settings. \\ \hline \multirow{4}{*}{_Risk of reactions_} & Although PEAS reactions are typically mild, the risk of unexpected systemic reactions necessitates close medical supervision. & Emergency treatments such as epinephrine must be readily available. \\ \hline \multirow{4}{*}{_Subjectivity_} & Open challenges may introduce bias, particularly for subjective symptoms like itching or tingling. & Blinded challenges (e.g., single- or double-blind) can help reduce bias. \\ \hline \multirow{4}{*}{_Patient anxiety_} & The prospect of consuming a suspected allergen can cause anxiety, which may complicate interpretation of symptoms. & Proper counseling and reassurance can help mitigate patient concerns before the challenge. \\ \hline \end{tabular}
\end{table} 
Table 4: Advantages and limitations of OFC in PFAS [98; 188; 194; 217; 218]. ulation. Unlike IgE, IgG\({}_{4}\) exhibits low affinity for Fc receptors on effector cells, preventing the activation of mast cells and basophils, and thereby mitigating allergic responses. IgG\({}_{4}\) is thought to act as a \"blocking antibody\" [221], competing with IgE for allergen binding and neutralizing allergens before they trigger an immune response. Increased levels of allergen-specific IgG\({}_{4}\) observed during successful OIT indicate a shift toward tolerance, with patients often experiencing reduced symptoms or complete desensitization [222; 223]. Similarly, IgA, particularly secretory IgA (slga), is integral to mucosal immunity and has been implicated in the pathophysiology of food allergy tolerance. Found predominantly in mucosal tissues such as the gastrointestinal tract, slga can form immune complexes with allergens, reducing their ability to cross the epithelial barrier and trigger an allergic response [224]. Elevated slga levels have been linked to protective effects against food allergy development and improved outcomes in OIT. For instance, studies have shown that salivary IgA levels correlate with positive therapeutic responses in peanut allergy OIT [224; 225]. The potential utility of measuring IgG\({}_{4}\) and IgA levels lies in their ability to serve as biomarkers for predicting and monitoring OIT success.