Evidence for the genetic control of immunoglobulin E reactivity to the allergens of Alternaria alternata

BACKGROUND: The fungus Alternaria alternata contains potent allergens, and sensitization to these allergens is associated with a high risk of respiratory disease. The influence of genetic regulation on sensitization to Alternaria is unknown. OBJECTIVE: To determine the influence of genetic factors on IgE responses to specific allergens of Alternaria. METHODS: The concordance of skin prick test (SPT), radioallergosorbent test (RAST) and IgE-binding profiles of sera were examined from a large cohort of monozygotic and dizygotic twins. RESULTS: Casewise concordance for a positive SPT response was monozygous (MZ) 66%: dizygous (DZ) 40% (P = 0.002). Logistic regression confirmed that casewise concordance was significantly stronger between MZ than DZ pairs. Immunoblotting against an Alternaria extract revealed 19 allergenic bands. The differences in concordance between the different bands were not significant for either the MZ (P = 0.97) or DZ (P = 0.84) groups. The pooled MZ : DZ difference in concordance was just significant (P = 0.049), suggesting an overall genetic effect on the response to Alternaria. This was reinforced by the comparison of the MZ and DZ correlations for total number of bands recognized (MZ r = 0.65; DZ r = 0.37, P = 0.015). Overall, there was a moderate correlation between the individual SPT weal size and RAST score (r(2) = 0.41) and a substantial correlation between the number of immunoblotted bands and RAST scores (r(2) = 0.79). CONCLUSION: There is a strong genetic influence on IgE response to the mixture of Alternaria allergens and a lesser effect on IgE response to individual allergens.