Anti-betalactoglobulin IgG antibodies bind to a specific profile of epitopes when patients are allergic to cow's milk proteins

Clin Exp Allergy. 1998 Jul;28(7):824-33. doi: 10.1046/j.1365-2222.1998.00314.x.


Background: We demonstrated recently that mite-allergic patients differed from healthy controls in the specificity of their IgG antibodies towards mite antigens.

Objective: The present study investigates whether these discriminatory IgG responses could be associated with the expression and the evolution of clinical manifestations in allergy to cow's milk proteins.

Methods: Antibody specificity was evaluated by comparing IgG-binding to native bovine beta-lactoglobulin (nBLG) and its products of pepsin hydrolysis (dBLG) using a solid-phase enzyme-linked immunosorbent assay (ELISA). Antibody specificity was further investigated in competitive ELISA using streptavidin-biotin technology with purified IgG fractions from selected subjects and specific mouse monoclonals raised against BLG.

Results: IgG antibodies from CM-intolerant or allergic sera (n=222) showed a higher degree of binding to nBLG than to dBLG, while control sera showed similar levels to both nBLG and dBLG (n=99 children/65 adults). Sera from symptomatic patients, wether or not they contained IgE antibodies, demonstrated group-segregating capacities to compete with pooled purified IgG from each clinical class, and with selected murine anti-nBLG monoclonal antibodies for binding to n- and dBLG. Furthermore, this inhibitory capacity shifted dramatically in a small subset (n=14) of children as they developed CM-tolerance.

Conclusions: The IgG responses to BLG of CM-intolerant or allergic patients are very different from those of healthy controls, being characterized not only by increased titres but also similar patterns of modified specificity, including a marked preference for conformational epitopes. Cross-competition experiments confirmed that the restricted specificity was clinically associated, appearing as an immunological signature, which allowed almost complete discrimination between patient groups. This phenomenon is a particularly promising diagnostic feature in this category of young patients where conventional tests usually only document the status of sensitization.

MeSH terms

  • Adult
  • Allergens / immunology
  • Animals
  • Antibodies / blood
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Biotinylation
  • Cattle
  • Child
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Immunoglobulin G / metabolism*
  • Lactoglobulins / immunology*
  • Lactoglobulins / metabolism*
  • Mice
  • Milk Hypersensitivity*
  • Milk Proteins / adverse effects*
  • Milk Proteins / immunology*


  • Allergens
  • Antibodies
  • Antibodies, Monoclonal
  • Epitopes
  • Immunoglobulin G
  • Lactoglobulins
  • Milk Proteins
  • Immunoglobulin E