European Journal of Nutrition

, Volume 49, Issue 8, pp 501–504 | Cite as

Specific antibodies to cow’s milk proteins in infants: effect of early feeding and diagnosis of cow’s milk allergy

  • Emma Merike Savilahti
  • Kristiina Mertta Saarinen
  • Erkki SavilahtiEmail author
Original Contribution



To investigate whether specific IgA, IgG, IgG1 and IgG4 responses to cow’s milk proteins differ between infants with cow’s milk allergy and infants with cow’s milk related symptoms (control subjects), and whether early feeding affects these responses as well as specific IgE.


A cohort of 6,209 healthy, full-term infants in a double-blind randomized trial received, as supplementary feeding at maternity hospitals (mean duration 4 days), either cow’s milk formula, extensively hydrolyzed whey formula or donor breast milk. Infants who developed cow’s milk associated symptoms (n = 223) underwent an open oral cow’s milk challenge (mean age 7 months), which confirmed cow’s milk allergy in 111 and was negative in 112. We measured in sera cow’s milk specific IgE levels with UniCAP (Phadia, Uppsala, Sweden), and β-lactoglobulin and α-casein specific IgA, IgG1, IgG4 and IgG levels with enzyme-linked immunosorbent assay.


Infants with IgE-mediated cow’s milk allergy had lower β-lactoglobulin and α-casein specific IgG1, IgG4 and IgG levels (p < 0.05) than infants with non-IgE-mediated cow’s milk allergy or control subjects. Within the group of infants with cow’s milk allergy, exposure to cow’s milk during the first few days after birth led to higher β-lactoglobulin and α-casein specific IgG4 levels (p < 0.005) compared to infants fed with either breast milk or extensively hydrolyzed formula.


Subdued IgG class responses to cow’s milk proteins characterized IgE-mediated cow’s milk allergy. In infants who developed cow’s milk allergy early exposure to cow’s milk resulted in a heightened specific IgG4 response.


α-Casein β-Lactoglobulin Cow’s milk allergy Infants’ feeding IgG4 Tolerance 



We are grateful to Elsa Valtonen and Terttu Louhio for their technical assistance in antibody measurements. We thank Helsinki University Central Hospital Research Funds and the Foundation for Pediatric Research for funding the study.


  1. 1.
    Saarinen KM, Juntunen-Backman K, Jarvenpaa AL, Kuitunen P, Lope L, Renlund M, Siivola M, Savilahti E (1999) Supplementary feeding in maternity hospitals and the risk of cow’s milk allergy: a prospective study of 6209 infants. J Allergy Clin Immunol 2(Pt 1):457–461Google Scholar
  2. 2.
    Jenmalm MC, Bjorksten B (1998) Exposure to cow’s milk during the first 3 months of life is associated with increased levels of IgG subclass antibodies to beta-lactoglobulin to 8 years. J Allergy Clin Immunol 4(Pt 1):671–678CrossRefGoogle Scholar
  3. 3.
    Juvonen P, Mansson M, Kjellman NI, Bjorksten B, Jakobsson I (1999) Development of immunoglobulin G and immunoglobulin E antibodies to cow’s milk proteins and ovalbumin after a temporary neonatal exposure to hydrolyzed and whole cow’s milk proteins. Pediatr Allergy Immunol 3:191–198CrossRefGoogle Scholar
  4. 4.
    Oldaeus G, Bjorksten B, Jenmalm MC, Kjellman NI (1999) Cow’s milk IgE and IgG antibody responses to cow’s milk formulas. Allergy 4:352–357CrossRefGoogle Scholar
  5. 5.
    Saarinen KM, Savilahti E (2000) Infant feeding patterns affect the subsequent immunological features in cow’s milk allergy. Clin Exp Allergy 3:400–406CrossRefGoogle Scholar
  6. 6.
    Tainio VM, Savilahti E, Arjomaa P, Salmenpera L, Perheentupa J, Siimes MA (1988) Plasma antibodies to cow’s milk are increased by early weaning and consumption of unmodified milk, but production of plasma IgA and IgM cow’s milk antibodies is stimulated even during exclusive breast-feeding. Acta Paediatr Scand 6:807–811CrossRefGoogle Scholar
  7. 7.
    Ruiter B, Knol EF, van Neerven RJ, Garssen J, Bruijnzeel-Koomen CA, Knulst AC, van Hoffen E (2007) Maintenance of tolerance to cow’s milk in atopic individuals is characterized by high levels of specific immunoglobulin G4. Clin Exp Allergy 7:1103–1110. doi: 10.1111/j.1365-2222.2007.02749.x CrossRefGoogle Scholar
  8. 8.
    Francis JN, James LK, Paraskevopoulos G, Wong C, Calderon MA, Durham SR, Till SJ (2008) Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J Allergy Clin Immunol 5:1120–1125.e2. doi: 10.1016/j.jaci.2008.01.072 CrossRefGoogle Scholar
  9. 9.
    Tomicic S, Norrman G, Falth-Magnusson K, Jenmalm MC, Devenney I, Bottcher MF (2008) High levels of IgG(4) antibodies to foods during infancy are associated with tolerance to corresponding foods later in life. Pediatr Allergy Immunol. doi: 10.1111/j.1399-3038.2008.00738.x
  10. 10.
    Saarinen KM, Pelkonen AS, Makela MJ, Savilahti E (2005) Clinical course and prognosis of cow’s milk allergy are dependent on milk-specific IgE status. J Allergy Clin Immunol 4:869–875. doi: 10.1016/j.jaci.2005.06.018 CrossRefGoogle Scholar
  11. 11.
    Savilahti E, Saukkonen TT, Virtala ET, Tuomilehto J, Akerblom HK (1993) Increased levels of cow’s milk and beta-lactoglobulin antibodies in young children with newly diagnosed IDDM. The Childhood Diabetes in Finland Study Group. Diabetes Care 7:984–989CrossRefGoogle Scholar
  12. 12.
    Punnonen J, Aversa G, Cocks BG, McKenzie AN, Menon S, Zurawski G, de Waal Malefyt R, de Vries JE (1993) Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci USA 8:3730–3734CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Emma Merike Savilahti
    • 1
  • Kristiina Mertta Saarinen
    • 1
  • Erkki Savilahti
    • 1
    Email author
  1. 1.Hospital for Children and Adolescents, University of HelsinkiHelsinkiFinland

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