D2.183 - Differential Sensitization to Goat and Sheep Milk with Partial Tolerance to Cow’s Milk

Cross-reactivity between mammalian milks is common due to the high structural similarity of caseins and whey proteins. However, cases of clinical tolerance or partial tolerance to cow's milk despite strong reactions to goat's and sheep's milk are becoming increasingly recognised, reflecting relevant biochemical differences in epitope conservation. 

We present the case of a patient who experienced a secondary loss of tolerance following the completion of cow's milk oral immunotherapy and now exhibits consistent symptoms upon ingesting dairy products.

The protein and allergen profiles of mammalian milk were analysed using SDS-PAGE and IgE-Western blotting under reducing conditions. An ELISA was performed to determine serum dilutions and a competitive ELISA was used to assess relative allergenic potency and cross-reactivity.

Specific IgE was detected for cow's milk (17.4 kU/L), α-lactalbumin (4.67 kU/L), β-lactoglobulin (0.22 kU/L), casein (27.4 kU/L), goat's milk (37.2 kU/L) and sheep's milk (46 kU/L). Western blot analysis revealed strong IgE binding to caseins in all samples, as well as additional reactivity to serum albumins, β-lactoglobulin and α-lactoalbumin. This is consistent with the patient’s serological profile. Binding was visibly stronger in goat's and sheep's milk than in cow's milk. An ELISA test confirmed higher antibody binding to sheep and goat extracts. A competitive ELISA test showed that sheep milk had the greatest allergenic potency and cow’s milk displayed minimal cross-reactivity. 

Our results confirmed cross-reactivity between goat's and sheep's milk, and substantially weaker immunological overlap with cow's milk. This correlates with persistent symptoms despite historical tolerance to cow's milk. In conclusion, Western blot analysis and competitive ELISA were essential for defining the allergenic relationships.