Scientific Study

Background: Patients exquisitely sensitive to cashew/pistachio are at risk for allergic reactions to citrus seeds and pectin. Objective: In this study, we sought to examine whether pectin is contaminated with citrus seeds, to identify a culprit antigen in citrus seeds, and to assess for cross-reactivity among allergens in citrus seeds, citrus pectin, and cashew/pistachio. Methods: Proteins from orange seed coats, orange seed endosperms, lemon seeds, grapefruit seeds, citrus pectin, apple pectin, and grapefruit pectin were extracted. Protein concentrations in all extracts were determined and visualized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels. IgE binding capacity was determined with Western blot analyses and Tandem Mass spectrometry (MS/MS) for the identification of the culprit allergen in citrus seeds and pectin. Results: In subjects with citrus seed, pectin, and cashew allergies, there was strong IgE-reactivity to bands between 17-28 kDa and 28-38 kDa. The MS/MS analysis of these bands indicated the presence of citrin as the culprit allergen. Citrin and Ana o 2 are both 11S globulins belonging to the cupin superfamily, and significant homology was demonstrated between these proteins. Conclusion: Citrus pectin may be contaminated with citrus seeds. Citrin, a newly identified allergen in citrus seeds, appears to be the culprit antigen in citrus seeds and contaminated citrus pectin. Citrin is highly homologous with Ana o 2 in cashew and Pis v 2 in pistachio, suggesting potential for cross-reactivity and providing an explanation for co-allergenicity of cashew/pistachio, citrus seeds, and citrus pectin. https://doi.org/10.1016/j.anai.2023.08.603