Lipid transfer protein (LTP) allergy is an emerging and significant cause of food-induced anaphylaxis in young adults in the Mediterranean region, including Spain, Italy, and southern France, where its prevalence may reach up to 60% among patients allergic to Rosaceae fruits.^1,2 These plant proteins are characteristically resistant to heat and gastric proteolysis, making them highly stable and capable of triggering severe systemic reactions even after ingestion of processed foods.³

Pru p 3, the LTP present in peach peel, is considered the prototype allergen of this group and the main trigger of clinical symptoms in sensitized individuals.⁴ In many cases, primary sensitization to Pru p 3 is associated with cross-reactivity to other plant LTPs found in nuts, legumes, and cereals, contributing to the clinical severity of the so-called “LTP syndrome.”⁵

Traditional management has focused on dietary avoidance. However, this does not prevent accidental exposures or improve patient quality of life. In recent years, sublingual immunotherapy (SLIT) has gained prominence as a therapeutic tool to induce clinical tolerance by modulating the adaptive immune response.⁶ Numerous studies have shown that SLIT can produce significant immunological changes, including reduction of specific IgE, increased blocking of IgG4, and induction of regulatory T cells (Tregs) and anti-inflammatory cytokines such as IL-10 and TGF-β.^7,8

Despite its growing use, SLIT is not universally effective and lacks robust predictors of clinical efficacy. Immunological biomarkers such as baseline total IgE, IgE specific to Pru p 3, and specific IgG4 have been proposed as potential predictors of tolerance induction.⁹ Moreover, the evolution of these parameters during treatment may indirectly reflect its immunological efficacy.

This study hypothesizes that baseline levels and posttreatment changes in total IgE, and IgE and IgG4 specific to Pru p 3 may predict clinical tolerance induced by SLIT.

A weak positive correlation was observed between baseline specific IgE to Pru p 3 and FAQLQ score (r = 0.28; P = 0.04), indicating that higher sensitization correlated with poorer quality of life.

An inverse moderate correlation was found between increased specific IgG4 and oral challenge reactivity (r = −0.42; P = 0.01), supporting its value as a tolerance marker.

Our findings support SLIT with peach extract as a safe and effective strategy to induce clinical tolerance in LTP syndrome. Higher baseline levels of total IgE, and specific IgE and IgG4 in tolerant patients suggest a more modifiable immune profile.^6,9

SLIT induces tolerance via several mechanisms, such as Treg activation, IL-10/TGF-β secretion, Th2-to-Th1 shift, and IgG4 blocking antibody production.^7,8 The increase in IgG4 in both groups reflects immunomodulatory exposure, though its predictive value is limited due to overlap in nontolerant patients.

Stabilization of specific IgE in tolerant patients versus its increase in nontolerant ones may serve as a more specific marker of a favorable response.

The correlation between specific IgE levels and FAQLQ scores confirms the clinical relevance of sensitization. Meanwhile, IgG4 rise correlated inversely with reactivity, suggesting a functional protective role.

These results align with previous studies, including Gómez et al.,⁹ who demonstrated that a low specific IgE/IgG4 ratio after SLIT correlates with tolerance. Future strategies may include functional biomarkers such as basophil activation tests and Treg profiling.¹³

SLIT appears to be a safe and potentially effective approach for LTP-induced anaphylaxis. We propose an immunological profile that may help select ideal candidates and guide monitoring. Further multicenter, controlled studies should validate these findings and incorporate advanced molecular biomarkers.

Ultra-rapid SLIT with standardized peach extract followed by a 12-month maintenance phase proved to be a safe and effective strategy for inducing clinical tolerance in patients with LTP-mediated anaphylaxis. The majority of patients tolerated the treatment and successfully passed the oral challenge, confirming the clinical benefit of this therapeutic approach.

Our findings suggest that patients who develop tolerance exhibit a more dynamic and responsive baseline immune profile, characterized by higher levels of total IgE, and IgE and IgG4 specific to Pru p 3. These patients also demonstrated a more favorable immunological evolution during treatment, particularly stabilization of specific IgE and a significant increase in blocking IgG4 antibodies.

The observed correlations between immunological parameters and clinical outcomes underscore the potential of serological biomarkers as tools for patient stratification and treatment monitoring. Specific IgG4 to Pru p 3, in particular, appears to be a promising indicator of immunological shift, though its predictive value is limited when used in isolation. Conversely, the lack of a significant increase in IgE and a greater IgG4 rise in tolerant patients support the utility of dynamic changes, rather than absolute values alone, in assessing treatment response.

These results highlight the importance of integrating immunological monitoring into routine clinical practice to guide decision-making and personalize therapy. The development of predictive algorithms based on serological markers, complemented by functional assays such as basophil activation tests or Treg cell profiling, could further refine patient selection and optimize SLIT outcomes.

Nonetheless, these findings must be interpreted in the context of a single-center study. Long-term, multicenter trials with larger populations and standardized protocols are essential to validate these results and incorporate advanced molecular and cellular biomarkers into allergy immunotherapy frameworks.

In summary, the integration of clinical outcomes with immunological profiling offers a promising path toward precision medicine in the management of LTP-mediated food allergy.