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

PURPOSE: 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. METHODS: 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 ß-lactoglobulin and α-casein specific IgA, IgG1, IgG4 and IgG levels with enzyme-linked immunosorbent assay. RESULTS: Infants with IgE-mediated cow's milk allergy had lower ß-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 ß-lactoglobulin and α-casein specific IgG4 levels (p < 0.005) compared to infants fed with either breast milk or extensively hydrolyzed formula. CONCLUSIONS: 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.

Markers of inflammation in the feces of infants with cow's milk allergy.

Growing evidence exists that exposure to cow's milk elicits inflammation in the gut of infants with cow's milk allergy, irrespective of symptoms. To demonstrate inflammation and increased protein leakage from the gut during a cow's milk elimination-challenge test in fecal samples of infants presenting with different symptoms suggestive of cow's milk allergy, we measured the concentrations of alpha1-antitrypsin (AT), eosinophil cationic protein (ECP), immunoglobulin (Ig) A, and cow's milk-specific IgA antibodies, in fecal samples of 208 infants with a mean age of 7 months. Prechallenge samples were collected after a mean 3-week elimination period, and post-challenge samples were obtained 4 days after starting the challenge. Fecal levels of prechallenge total IgA (p = 0.02) and post-challenge AT (p = 0.001) were higher in infants with a positive challenge. Of these infants, pre- and post-challenge levels of ECP were higher in those reacting after 24 h than in those reacting within 1 h (p = 0.006 and p = 0.045). Prechallenge levels of ECP were higher in those showing intestinal symptoms (p = 0.008), and both pre- and post-challenge levels of total IgA were higher in those with an IgE-mediated reaction to cow's milk (p = 0.04 and p = 0.008). Regardless of the challenge result, total IgA increased during the challenge (p < 0.001 for both challenge-positive and -negative infants) and was higher in those breast-fed until the challenge than in those fed formula only (p < 0.01). Hence, in infants reacting to the cow's milk challenge, higher prechallenge levels of fecal IgA indicate increased antigenic stimuli in the gut, and higher post-challenge levels of AT reflect increased protein loss as a result of intestinal inflammation. In infants with slowly evolving gastrointestinal symptoms, increased fecal ECP may help in distinguishing patients from those who tolerate cow's milk. Individual serial follow-up of fecal IgA and ECP can be used to estimate the degree of inflammation in the gut and an appropriate time for a challenge test, but are not diagnostic tools for cow's milk allergy.