Random outcomes of allergen-specific responses in atopic families

Background: Allergens are common non-infectious antigens to which people will mount T cell dependent humoral responses. Among genetically susceptible individuals, an antigen-specific response results involving the production of allergen-specific IgE (atopy). Objective: Determine if this susceptibility is manifested as an inherited, allergen-specific trait or a random response to allergens among susceptible people. Methods: We evaluated allergen-specific outcomes in 1099 members of families with positive atopic history (26 multi-generation and 112 nuclear families). Each was tested for sensitivity to 14 common allergens by standardized skin prick test (SPT), a marker of specific IgE production. Over 15000 individual SPT's were evaluated. Among five randomly selected multi-generation families (N = 163), semi-quantitative determinations of Amb a 1-specific IgA1,2 and IgGl-4 were determined in three groups: (A) Amb a SPT⁺/Amb a 1-IgE⁺, (B) Amb a SPT^-/Amb a 1-IgE⁺, (C) Amb a SPT^-/Amb a 1-IgE^-. Results: By rank correlation statistics, there were no discernible 'patterns' of specific SPT outcomes among any of the multi-generation families, suggesting that environmental exposure rather than allergen-specific inheritance determined the responses. This was confirmed among the nuclear families since the conditional SPT outcomes among children were independent of the SPT responses of their parents. Among five randomly selected multi-generation families, the relative proportionate concentrations of the Amb a 1-specific IgA and IgG subclasses were comparable, regardless of atopic sensitization to the ragweed allergen Amb a. Conclusion: While the general propensity for atopy may be inherited, an individual's specific atopic outcome is a random variable independent of familial sensitization patterns.