Cross-sensitization between Cannabis sativa and Lipid transfer proteins: Evidence from a large molecular cohort.

Frias Ruiz C.; Martin Martinez M.; Garcia de la Rosa G. · Allergy and asthma proceedings · 2026

**Background & Methods** This retrospective observational study evaluated 2,409 patients referred for allergological evaluation to characterize sensitization patterns to Cannabis sativa allergen Can s 3 and its cross-reactivity with food- and pollen-derived nonspecific lipid transfer proteins (nsLTP). Allergen-specific immunoglobulin E (IgE) was measured using multiplex allergen-specific IgE platform, with sensitization defined as specific IgE ≥0.35 kUA/L. Statistical analyses included Fisher exact test with odds ratios, Spearman correlation, principal component analysis, and k-means clustering. **Key Findings** • Overall, 35.0% of patients demonstrated sensitization to at least one nsLTP component. Can s 3 sensitization showed exceptionally strong associations with food-derived nsLTPs, particularly peach (Pru p 3) and apple (Mal d 3) with odds ratios of 222.9 and 227.6, respectively (p < 0.001). • Can s 3 sensitization rarely occurred in isolation; instead, it was consistently part of a broader polysensitization pattern involving multiple nsLTP allergens from both food and pollen sources, indicating integrated cross-reactivity networks. • The findings support a shared nsLTP-mediated cross-reactivity mechanism and suggest that Can s 3 should be included in molecular diagnostic panels for suspected nsLTP-mediated allergic reactions. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Not reported. The study mentions that nsLTP allergens are associated with systemic allergic reactions; however, specific adverse events or clinical manifestations in this cohort were not detailed in the abstract. **Evidence Quality** This is a retrospective observational study without a control group, limiting causal inference. Strengths include a large molecular cohort (n=2,409) and comprehensive statistical analysis using multiple approaches. However, the study design cannot establish causality and may be subject to selection bias given the population consisted of patients referred for allergological evaluation. The molecular approach using multiplex allergen-specific IgE is robust, but clinical correlation and symptom-based outcomes were not reported. The study represents moderate evidence for associations between Can s 3 and nsLTP sensitization patterns but requires prospective validation and clinical correlation to establish clinical significance.

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