Diagnostic significance of inflammation biomarkers in the gastrointestinal form of food allergy in early age children
GASTROENTEROLOGY AND DIETOLOGY
Abstract
Introduction.Gastrointestinal forms of food allergy in early childhood are characterized by clinical heterogeneity and diagnostic challenges, highlighting the need for reliable biomarkers of inflammation and intestinal barrier dysfunction.The aim— to assess the diagnostic and differential diagnostic value of fecal inflammatory and intestinal permeability markers (eosinophil-derived neurotoxin, calprotectin, and zonulin) in combination with total Ig E for distinguishing major gastrointestinal forms of food allergy in young children.Materials and methods.A total of 130 children aged 3 months to 3 years with gastrointestinal food allergy (mean age 11.7±1.5 months) were examined at the Republican Specialized Scientific and Practical Medical Center of Pediatrics. Group I included 76 children with allergic enterocolitis, and Group II consisted of 54 children with allergic enteropathy. The control group comprised 45 healthy age-matched children. Fecal levels of eosinophil-derived neurotoxin (EDN), calprotectin, and zonulin were measured using enzyme-linked immunosorbent assays, along with serum total Ig E.Results.Children with allergic enteropathy demonstrated significantly elevated total Ig E and fecal EDN levels, indicating predominantly Ig E-mediated eosinophilic inflammation, while fecal zonulin levels were relatively lower. In contrast, allergic enterocolitis was associated with marked increases in fecal calprotectin and zonulin, reflecting activation of innate immune inflammation and impaired intestinal barrier function.Conclusion.Combined assessment of fecal inflammatory and intestinal permeability biomarkers together with total Ig E improves diagnostic accuracy and facilitates differentiation of gastrointestinal forms of food allergy in young children
References
1. Cook V.E., Connors L.A., Vander Leek T.K., Watson W. Non-Ig E-mediated food allergy. Allergy Asthma Clin Immunol. 2024;20(Suppl 3):70. https://doi.org/10.1186/s13223-024-00933-4.
2. Labrosse R., Graham F., Caubet J.C. Non-Ig E-mediated gastrointestinal food allergies in children: an update. Nutrients. 2020;12(7):2086. https://doi.org/10.3390/nu12072086.
3. Moghtaderi-Mostafavi M., Mehrabi Y., Pourpak Z., Rezaei N. Sensitization to common food allergens in infants with food protein-induced allergic proctocolitis. Asia Pac Allergy. 2025;15(3):171–175. https://doi.org/10.5415/apallergy.0000000000000182.
4. Carucci L., Nocerino R., Coppola S. et al. Factors influencing the natural course of non-Ig E-mediated gastrointestinal food allergies in children: a prospective multicenter cohort study. BMJ Paediatr Open. 2025;9(1):e003203. https://doi.org/10.1136/bmjpo-2024-003203. Erratum in: BMJ Paediatr Open. 2025;9(1):e003203corr1. https://doi.org/10.1136/bmjpo-2024-003203corr1.
5. González-Delgado P., Entrala A., Nuñez-Orjales R. et al. Food proteininduced enterocolitis syndrome in adults: review and practice recommendations. Explor Asthma Allergy. 2024;(2):148–60. https://doi.org/10.37349/eaa.2024.00036.
6. Tran K.L., Wisner E.L., Jeha G.M., Wall L.A. Development of Ig E-mediated food allergy in children with a history of food protein-induced allergic proctocolitis: a case series. Front Allergy. 2024;5:1354106. https://doi.org/10.3389/falgy.2024.1354106.
7. Cianferoni A. Non-Ig E-mediated food allergy. Curr Pediatr Rev. 2020;16(2):95–105. https://doi.org/10.2174/1573396315666191031103714.
8. Vandenplas Y., Broekaert I., Domellöf M. et al.; ESPGHAN Working Group. An ESPGHAN position paper on the diagnosis, management, and prevention of cow’s milk protein allergy. J Pediatr Gastroenterol Nutr. 2024;78(2):386–413. https://doi.org/10.1097/MPG.0000000000003897.
9. Мозжухина Л.И., Кисельникова О.В., Салова А.Л. Гастроинтестинальные проявления пищевой аллергии у детей раннего возраста: клинические формы, диагностика и прогноз. Пациентоориентированная медицина и фармация. 2025;3(3):50–54. https://doi.org/10.37489/2949-1924-0102.
10. Бойцова Д.А. Изменения гастроинтестинальных проявлений и уровней фекального кальпротектина при пищевой аллергии у детей первого года жизни. Российский педиатрический журнал. 2024;27(4S):16. EDN: odwpwl.
11. Приходченко Н.Г., Шуматова Т.А., Коваленко Д.В. Фекальный уровень зонулина как прогностический маркер атопического марша у детей с пищевой аллергией. Аллергология и иммунология в педиатрии. 2024;(3):31–41. https://doi.org/10.53529/2500-1175-2024-3-31-41.
12. Vandenplas Y., Salvatore S., Ribes-Koninckx C. et al. The Cow’s milk-related symptom score (Co Mi SS™): update 2022. Nutrients. 2022;14(13):2682. https://doi.org/10.3390/nu14132682.
13. Kunz B., Oranje A.P., Labreze L., Stalder J.F., Ring J., Taïeb A. Clinical validation and guidelines for the SCORAD index: consensus report. Dermatology. 1997;195(1): 10–19. https://doi.org/10.1159/000245677.
14. Anania C., Mondì F., Brindisi G. et al. Fecal calprotectin determination in a cohort of children with cow’s milk allergy. Nutrients. 2025;17(1):194. https://doi.org/10.3390/nu17010194.
15. Czaja-Bulsa G., Bulsa K., Łokieć M., Drozd A. Can fecal zonulin and calprotectin levels be used for diagnosis and monitoring in infants with food protein-induced allergic proctocolitis? Nutrients. 2024;16(17):2949. https://doi.org/10.3390/nu16172949.
16. Sun T., Virkud Y.V., Kirpas M. et al. Fecal calprotectin and other biomarkers did not show prospective association with food protein-induced allergic proctocolitis. J Pediatr Gastroenterol Nutr. 2026;82(1):42–49. https://doi.org/10.1002/jpn3.70257.
