Precision Medicine in Plant Food Allergy: a Systematic Review of Biomarkers Under a Clinical Approach

Plant food allergy (FA) is a major global health problem, being peanut one of the most studied allergenic foods worldwide. Biomarkers (Bms) are essential tools for precision medicine, guiding diagnosis, risk stratification, and treatment. However, evidence on their clinical applicability in plant FA remains limited and fragmented. Therefore, we aim to systematically review the Bms identified in plant FA related to several aspects of the pathology. This systematic review was performed in accordance with the PRISMA guidelines. A comprehensive search was conducted in three databases (PubMed, Web of Sciences and Cochrane Library) between July 2019 and July 2024. Articles were screened using predefined inclusion and exclusion criteria, and categorized into five thematic sections: sensitization, tolerance, threshold, severity and follow-up treatment. Risk-of-bias and certainty of evidence were assessed using validated tools and the GRADE approach. From the 733 articles found, 71 studies met inclusion criteria and were selected for data extraction. A majority of them were high-quality publications and predominantly involved pediatric cohorts from Europe and North America. Peanut was the most studied food, followed by nuts and wheat, while fruits and seeds were rarely represented. Across all sections, most of the studies were related to severity and tolerance. Specific IgE to whole extracts or molecular components were the most frequent Bms, followed by skin prick test. Emerging Bms were identified, although they remain in early validation stages. Risk-of-bias and certainty of evidence were primarily moderate, reflecting the exploratory nature of most of the included studies. This review highlights the predominance of classical Bms and the promise of novel candidates for future clinical integration. However, research remains allergen-, age- and region-restricted, underscoring the need for multicenter studies, representative patient samples, and validation of emerging Bms to achieve globally applicable precision medicine in plant FA.