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. 2024 Dec;96(7):1812-1821.
doi: 10.1038/s41390-024-03260-x. Epub 2024 May 27.

Serum eosinophil-derived neurotoxin: a new promising biomarker for cow's milk allergy diagnosis

Wael A Bahbah  1 , Ahmed S Abo Hola  1 , Hanan M Bedair  2 , Eman T Taha  3 , Heba M S El Zefzaf  4
Affiliations

Serum eosinophil-derived neurotoxin: a new promising biomarker for cow's milk allergy diagnosis

Wael A Bahbah et al. Pediatr Res. 2024 Dec.

Abstract

Background: Cow's Milk Allergy (CMA) diagnosis is often a challenge due to the non-specific nature of symptoms and lack of a confirmatory diagnostic test. To our knowledge no previous studies investigated serum Eosinophil-Derived Neurotoxin (sEDN) in CMA. So, we aimed to assess the role of sEDN in CMA diagnosis.

Methods: Forty-five infants with CMA were compared to 45 infants with functional gastrointestinal disorders (FGIDs) and 45 healthy controls. For all participants, Cow's Milk-related Symptom Score (CoMiSS) was documented, and sEDN level with hematological parameters were measured before starting elimination diet.

Results: Receiver operation characteristic (ROC) curve identified sEDN > 14 ng/mL and CoMiSS > 9 as the optimal cut-off points to discriminate CMA from other groups with sensitivity 86.67%, 97.78% and specificity 60.00%, 78.89% respectively. Additionally, absolute neutrophil count (ANC) showed the highest sensitivity and specificity (80.0% and 78.89%) among hematological parameters. Although CoMiSS and ANC showed a significant positive correlation with sEDN in CMA group, CoMiSS was the only significant predictor for sEDN in multivariate linear regression.

Conclusions: sEDN showed high sensitivity in discriminating infants with and without CMA. Therefore, it is suggested as a potential biomarker for CMA diagnosis. Also, ANC should be closely monitored in these infants.

Impact: CMA presents with high heterogeneity, which complicates the diagnosis especially non-IgE-mediated and mixed types. So, oral food challenge continues to be the gold standard for its diagnosis. ROC curve identified CoMiSS > 9 as the best cut-off point to identify CMA. However, CoMiSS is a good awareness tool for CMA but not a diagnostic tool. sEDN level was significantly higher in infants with CMA with a good diagnostic performance in differentiating them than those without CMA. So, it is suggested as a potential biomarker for CMA diagnosis. ANC could have a role in CMA diagnosis and differentiating it from FGIDs.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval: The present study was approved by the Institutional Review Boards (IRB) of the Menoufia Faculty of Medicine in accordance with the Helsinki Declaration of Principles (ID number : 11/2022 PEDI 23). Our participants completed the study after a written consent from their parents/guardians. Informed consent: Informed consent was obtained from all the legally authorized representatives of participants included in the study.

Figures

Fig. 1
Fig. 1. ROC curve for total CoMiSS.
ROC curve identified the score of > 9 as the best cut-off point to discriminate CMA group (n = 45) vs FGIDs and Control groups (n = 90). Area under the curve (AUC): 0.964, with a sensitivity of 97.78%, specificity of 78.89%, PPV of 69.8, and NPV of 98.6.
Fig. 2
Fig. 2. ROC curve for hematological parameters.
ROC curve analysis of hematological parameters to discriminate CMA group (n = 45) vs FGIDs and Control groups (n = 90) revealed high sensitivity and specificity of ANC (sensitivity 80%, specificity 78.89%, and AUC: 0.909). In contrast, NLR, TLC, MPV and ALC showed low sensitivity and specificity (sensitivity 0.71.11%, 66.67%, 62.22% and 60%, specificity 58.89%, 53.33%, 53.33%, and 53.33% respectively).
Fig. 3
Fig. 3. Serum Eosinophil-Derived Neurotoxin level among the 3 studied groups.
Median (IQR) of sEDN (ng/mL) in the 3 studied groups.
Fig. 4
Fig. 4. ROC curve for serum eosinophil-derived neurotoxin.
ROC curve identified the score of > 14 ng/mL as the best cut-off point to discriminate CMA group (n = 45) vs FGIDs and Control groups (n = 90). Area under the curve (AUC): 0.754, with 86.67% sensitivity, 60.00% specificity, PPV of 52.0, and NPV of 98.6.
Fig. 5
Fig. 5. Correlation between Serum Eosinophil-Derived Neurotoxin and CoMiSS.
A significant positive spearman’s coefficient correlation was observed between sEDN and CoMiSS
See this image and copyright information in PMC

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