Mutations in the high-affinity IgE receptor β-chain are not associated with nonresponder status

Background: Basophils of some individuals do not release histamine upon activation of their high-affinity immunoglobulin E (IgE) receptor (Fc(epsilon)RI), but do so if this receptor is circumvented for cell activation. This so-called nonresponder phenomenon is clinically relevant, because in various studies atopy was less frequent or absent in nonresponder individuals. So far, it is unknown if this phenomenon is acquired during adulthood or exists from birth on. Methods: Histamine release was determined from isolated leucocytes stimulated with anti-IgE or calciumionophor. Also, random primed cDNA was synthesized and the open reading frame (ORF) of the Fc(epsilon)RI beta-subunit amplified and sequenced. Results: In the first part of our study, we examined the role of atopic status, type of atopy, and age in a random population of 95 children of whom we found 22% to be nonresponder. None of these parameters correlated with the nonresponder status. Except for food allergy, no specific type of atopy correlated with histamine release. The mechanism underlying the nonresponder phenomenon is assumed to occur early in the signalling cascade. We hypothesized that mutations in the Fc(epsilon)RI beta-chain may be associated with the nonresponder status, and in the second part of our study sequenced the beta-subunit in 20 responders and 20 nonresponders. Two conservative and two nonconservative heterozygous one base mutations (Thr179Thr, Asp216Asp, Ile147Leu and Glu237Gly) were found in two nonresponders and one responder. Three of these mutations have not been described so far. Conclusion: The nonresponder phenomenon is present from birth on and genetically determined. In our population, it was not associated with age or the presence of atopy, and appeared not to be caused by mutations in the Fc(epsilon)RI beta-chain.