Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy.

Tolerance to allergens may partly depend on allergen-specific IgG and IgG subclasses and IgA antibodies. We investigated whether specific IgG and IgG subclasses and IgA antibodies to β-lactoglobulin, α-casein, and ovalbumin differed between infants who had verified cow's milk allergy (CMA) and infants with cow's milk (CM)-associated eczema, but negative CM oral challenge. The study population comprised 95 infants with clinical eczema that was by history associated with the consumption of CM. After an elimination period, a double-blind, placebo-controlled (DBPC) CM oral challenge confirmed CMA in 45 infants. Skin prick tests (SPT) were performed with CM and hen's egg. Serum levels of IgE antibodies to CM and hen's egg were measured with UniCAP (Phadia, Uppsala, Sweden), and levels of IgA, IgG, IgG1, and IgG4 antibodies to β-lactoglobulin, α-casein, and ovalbumin were measured with enzyme-linked immunosorbent assay. We observed that infants with CMA had lower IgG4 levels to β-lactoglobulin than infants with negative DBPC CM challenge (p = 0.004). Positive CM SPT was associated with lower IgG4 levels to α-casein (p = 0.04). The relation of CM IgE to β-lactoglobulin and α-casein IgG4 was higher in CMA than in infants with negative challenge (p < 0.002 and 0.0001). Positive egg SPT was associated with elevated levels of specific IgG to ovalbumin, β-lactoglobulin, and α-casein as well as IgA to α-casein (p < 0.04). Our study thus shows that low β-lactoglobulin-specific serum IgG4 levels may differentiate eczematous infants with CMA from infants who have eczema with only suspected association with CM.