Comment on “Clinical characteristics and IgE-binding protein profiles of patients with buckwheat allergy in China”

Dear Editor,

We read with great interest the study by Bian et al. examining the clinical characteristics and immunoglobulin E (IgE)-binding protein profiles of patients with buckwheat allergy in China.¹ The authors should be commended for addressing an understudied food allergy and for exploring molecular sensitization patterns associated with distinct clinical phenotypes. Their identification of a potential association between sensitization to the 22–24 kDa protein and buckwheat husk allergy provides valuable insight into the heterogeneity of allergic responses to buckwheat. Nevertheless, several additional considerations may influence the interpretation and translational applicability of the findings.

A notable concern relates to the diagnostic framework used to define buckwheat allergy. The diagnosis relied primarily on clinical history combined with positive specific IgE testing and/or skin prick testing. Although this approach reflects routine clinical practice, the absence of standardized oral food challenge confirmation introduces uncertainty regarding the true clinical relevance of sensitization patterns. This issue is particularly important because sensitization does not invariably equate to clinically significant allergy. The observed association between the 22–24 kDa protein and respiratory manifestations could therefore partly reflect immunologic sensitization rather than genuine disease expression. From a clinical perspective, the distinction between sensitization and symptomatic allergy is critical because molecular markers intended for risk stratification must ultimately predict reproducible clinical outcomes rather than laboratory reactivity alone.

Another issue concerns the interpretation of the logistic regression model used to identify factors associated with buckwheat husk allergy. The final model included positivity for the 22–24 kDa protein and f11-specific IgE levels; however, several potentially relevant covariates were not incorporated despite their biological plausibility. Allergic rhinitis, asthma, concomitant food allergy, total IgE concentration, and other atopic comorbidities were common within the cohort and may influence both inhalational sensitization and respiratory symptom development.² Because respiratory reactions to buckwheat husks occurred predominantly in patients with asthma, residual confounding remains possible. Consequently, the reported odds ratio of 5.22 may not fully represent an independent protein-specific effect. Future analyses incorporating broader atopic and environmental variables may provide a more robust assessment of whether the identified protein contributes directly to respiratory allergy or serves as a surrogate marker of an atopy-prone phenotype.

The study also highlights an important but insufficiently explored discrepancy between immunologic findings and clinical severity. Despite a remarkably high rate of anaphylaxis, neither f11-specific IgE concentrations nor most identified protein bands demonstrated meaningful associations with severe reactions. This finding suggests that mechanisms beyond simple allergen-specific IgE burden may contribute to clinical severity. Factors such as allergen epitope diversity, IgE affinity, mast-cell activation thresholds, basophil responsiveness, and cofactor-dependent augmentation of allergic reactions may be equally important determinants of anaphylaxis risk.³ Without integrating functional assays such as basophil activation testing or inhibition studies, it remains difficult to determine whether the identified proteins are merely markers of sensitization or active drivers of pathogenic immune responses.⁴ This distinction has substantial implications for the development of future component-resolved diagnostic strategies.

An additional translational consideration involves the substantial coexistence of respiratory allergy and food-induced reactions within the cohort. The findings raise the possibility that buckwheat allergy may represent a spectrum of mucosal sensitization pathways rather than discrete ingestion-related and inhalational disorders. However, exposure intensity, occupational contact, household environmental burden, and pillow-use history were not systematically evaluated. These exposure-related variables may influence sensitization trajectories and could help explain why only a subset of patients developed respiratory manifestations. Incorporating quantitative exposure assessments into future studies may improve understanding of disease evolution and identify modifiable environmental risk factors.

The work by Bian et al advances knowledge regarding the molecular landscape of buckwheat allergy and provides an important foundation for component-based phenotyping. Integrating clinically confirmed allergy outcomes, comprehensive atopic covariates, functional immunologic testing, and exposure characterization may further refine the relationship between allergen components and disease expression. Such efforts could facilitate more precise risk stratification and strengthen the clinical utility of molecular diagnostics in buckwheat allergy.

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CRediT author statement

Madhuri Tribhuvan: Validation, Supervision, Project Administration, Writing—Original Draft, Writing—Review & Editing.

Shashikant N. Phatke: Conceptualization, Methodology, Writing—Original Draft, Writing—Review & Editing.

All authors reviewed and approved the manuscript.

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work the authors used Grammarly and ChatGPT in order to refine language, grammar, and style. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

Conflict of interests

The authors declare no conflict of interests relevant to this study.