European Journal of Nutrition

, Volume 52, Issue 2, pp 637–646 | Cite as

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

  • Tamara Pozo-Rubio
  • Amalia Capilla
  • Jorge R. Mujico
  • Giada de Palma
  • Ascensión Marcos
  • Yolanda Sanz
  • Isabel Polanco
  • Maria Dolores García-Novo
  • Gemma Castillejo
  • Carmen Ribes-Koninckx
  • Vicente Varea
  • Francesc Palau
  • Luis Ortigosa
  • Luis Peña-Quintana
  • Esther NovaEmail author
Original Contribution



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.


Lymphocyte subsets Coeliac disease Infants HLA genotype Breastfeeding Formula feeding 



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



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).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Tamara Pozo-Rubio
    • 1
  • Amalia Capilla
    • 2
  • Jorge R. Mujico
    • 1
  • Giada de Palma
    • 3
  • Ascensión Marcos
    • 1
  • Yolanda Sanz
    • 3
  • Isabel Polanco
    • 4
  • Maria Dolores García-Novo
    • 5
  • Gemma Castillejo
    • 6
  • Carmen Ribes-Koninckx
    • 7
  • Vicente Varea
    • 8
  • Francesc Palau
    • 2
  • Luis Ortigosa
    • 9
  • Luis Peña-Quintana
    • 10
  • Esther Nova
    • 1
    Email author
  1. 1.Immunonutrition Group, Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN)Spanish National Research Council (CSIC)MadridSpain
  2. 2.Instituto de Biomedicina de Valencia (CSIC) and CIBER de Enfermedades Raras (CIBERER)ValenciaSpain
  3. 3.Microbial Ecophysiology and Nutrition Group, Institute of Agrochemistry and Food TechnologySpanish National Research Council (IATA-CSIC)ValenciaSpain
  4. 4.Gastroenterology and Paediatric Nutrition ServiceHospital Universitario La PazMadridSpain
  5. 5.Gastroenterology UnitHospital Universitario Infantil Niño JesúsMadridSpain
  6. 6.Paediatric Gastroenterology UnitHospital Universitari Sant Joan de Reus, Universitat Rovira i VirgiliTarragonaSpain
  7. 7.Gastroenterology UnitHospital Infantil Universitario La FeValenciaSpain
  8. 8.Paediatric Gastroenterology, Nutrition and HepatologyHospital Universitario Sant Joan de Deu BarcelonaBarcelonaSpain
  9. 9.Gastroenterology, Hepatology and Nutrition UnitHospital Universitario Nuestra Señora de Candelaria, Santa Cruz de TenerifeCanary IslandsSpain
  10. 10.Nutrition Research Group, Department of Clinical Sciences, Centre for Health SciencesUniversity of Las Palmas de Gran CanariaLas PalmasSpain

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