The establishment of cow's milk protein allergy in infants is related with a deficit of regulatory T cells (Treg) and vitamin D

Pediatr Res. 2017 May;81(5):722-730. doi: 10.1038/pr.2017.12. Epub 2017 Jan 18.


Background: Cow's milk protein allergy (CMPA) is the most common food allergy in infants. However, little is known about which specific immune mechanisms are related with the CMPA onset. The objective was to investigate which immune alterations constitute differential factors between allergy and tolerance, and hence could be implicated in the CMPA establishment in infants.

Methods: An extensive analysis of immune subsets, including Treg and cytokine-secreting cells was performed in blood samples from 28 infants younger than 9 mo obtained 1-4 d after the first adverse reaction to milk.

Results: Less than 4 d after first allergic reaction, infants who developed CMPA had decreased Treg counts and increased frequency of IL4-secreting CD4 T cells compared to controls. The deficit of Tregs was correlated with decreased serum levels of vitamin D. Values of Tregs, IL4-secreting cells and vitamin D were good predictors of CMPA diagnosis. Basal vitamin D levels in CMPA infants also predicted those CMPA patients developing spontaneous tolerance in the first year.

Conclusion: Establishment of CMPA in infants was related with lower Treg and vitamin D levels. These immune alterations would be crucial factors behind the CMPA establishment and they could constitute a therapeutic target for treatment of CMPA.

MeSH terms

  • Area Under Curve
  • Biomarkers / blood
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Humans
  • Infant
  • Interleukin-4 / blood
  • Milk Hypersensitivity / blood
  • Milk Hypersensitivity / diagnosis
  • Milk Hypersensitivity / immunology*
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • ROC Curve
  • Risk Factors
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Time Factors
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / diagnosis
  • Vitamin D Deficiency / immunology*


  • Biomarkers
  • IL4 protein, human
  • Vitamin D
  • Interleukin-4