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Influence of breastfeeding versus formula feeding on lymphocyte subsets in infants at risk of coeliac disease: the PROFICEL study



In addition to genetic risk, environmental factors might influence coeliac disease (CD) development. We sought to assess the effect of the interaction between milk-feeding practices and the HLA-DQ genotype on peripheral lymphocyte subsets and their activation markers in infants at familial risk for CD.


170 newborns were classified in 3 different genetic risk groups (high risk, HR; intermediate risk, IR; and low risk, LR) after DQB1 and DQA1 typing. Lymphocyte subsets were studied at the age of 4 months by flow cytometry analysis.


79 infants were receiving exclusive breastfeeding (BF) and 91 partial breastfeeding or formula feeding (FF). Regarding genetic risk, 40 infants were classified in HR group, 75 in IR group and 55 in LR group. Two-way ANOVA did not show significant interactions between the type of milk feeding and genetic risk group on the lymphocyte subsets analysed. One-way ANOVA for milk-feeding practice alone showed that the percentage of CD4 + CD25+ cells was significantly higher in BF group than in FF group (BF, 10.92 ± 2.71; FF, 9.94 ± 2.96; p = 0.026), and absolute counts of CD4 + CD38+ cells were significantly higher in FF group than in BF group (FF, 2,881.23 ± 973.48; BF, 2,557.95 ± 977.06; p = 0.038). One-way ANOVA for genetic risk alone showed that absolute counts of NK cells were significantly higher in IR group than HR and LR groups (IR, 539.24 ± 340.63; HR, 405.01 ± 239.53; LR, 419.86 ± 262.85; p = 0.028).


Lymphocyte subset profiles in the early stages of life could be modulated by milk-feeding practices and genetic risk separately. Breastfeeding might have a positive immunomodulatory effect on lymphocyte subsets in infants at risk of CD.

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Fig. 1



Coeliac disease


Polymerase chain reaction-sequence-specific primers


Human leucocyte antigen


Regulatory T cells


Natural killer


Low genetic risk


Intermediate genetic risk


High genetic risk




Formula/mixture feeding


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We gratefully acknowledge the assistance of the statistician Dr. Laura Barrios in the statistical analysis. Supported by grants AGL2007-66126-C03-01/ALI, AGL2007-66126-C03-02/ALI and AGL2007-66126-C03-03/ALI, from the Spanish Ministry of Science and Innovation and grants 200570F0091 and 200570F0093 from CSIC. T. Pozo and G. de Palma were recipients of a personal grant from the JAE/I3P Program of CSIC (Spain).

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The authors declare that they have no conflict of interest.

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Correspondence to Esther Nova.

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Pozo-Rubio, T., Capilla, A., Mujico, J.R. et al. Influence of breastfeeding versus formula feeding on lymphocyte subsets in infants at risk of coeliac disease: the PROFICEL study. Eur J Nutr 52, 637–646 (2013).

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  • Lymphocyte subsets
  • Coeliac disease
  • Infants
  • HLA genotype
  • Breastfeeding
  • Formula feeding