ADCC-mediating capacity in children with cow's milk protein intolerance in relation to IgG subclass profile of serum antibodies to beta-lactoglobulin.

Abstract

In a previous study sera from children with cow's milk protein intolerance (CMPI) exhibiting gastrointestinal symptoms were found to efficiently induce antibody-dependent cell-mediated cytotoxicity (ADCC) to beta-lactoglobulin-coated cells. In contrast, sera from children with coeliac disease showed a low ADCC-mediating capacity, despite high levels of IgG anti-beta-lactoglobulin antibodies. The study described here was undertaken to evaluate whether differences in IgG subclass profile of anti-beta-lactoglobulin antibodies could explain the observed variations in the ADCC-mediating capacity. Forty-eight sera from the following groups of children were investigated: CMPI with predominantly gastrointestinal symptoms, CMPI with skin symptoms of immediate-onset, children with untreated coeliac disease and healthy references. Absorption experiments indicated that primarily IgG1 antibodies were responsible for the ADCC-mediating capacity of the sera. Accordingly, the ADCC reactivity of individual sera correlated with their IgG1 antibody levels. Sera from CMPI children with gastrointestinal symptoms, most of which had a high ADCC reactivity, also demonstrated a distinctive subclass pattern of their anti-beta-lactoglobulin antibodies with higher relative proportions of IgG1 (ratios: IgG1/IgG, IgG1/IgG3 and IgG1/IgG4) than those from the other diagnostic groups. Using logistic regression analysis, the diagnostic potential of ADCC as well as of different IgG subclass variables for the recognition of gastrointestinal symptoms caused by CMPI was evaluated. The ADCC reactivity of sera was found to be the best predictor in this model.