Syk deficiency in nonreleaser basophils

Background: Peripheral blood basophils from 10% to 20% of donors fail to degranulate in response to cross-linking the high-affinity IgE receptor Fc epsilon RI, The molecular mechanisms underlying the nonreleaser phenotype have not been established, Objectives: Our aim was to compare the expression of Fc epsilon RI-associated protein tyrosine kinases between nonreleaser and releaser basophils, Methods: With use of Western blotting we investigated Syk and Lyn protein levels in highly purified basophils from 3 anti-IgE nonreleasers and 2 releasers, Results: We identified 3 healthy nonatopic donors whose nonreleaser basophils express Fc epsilon RI normally but fail to express protein for the tyrosine kinase Syk, which is implicated in the initiation of Fc epsilon RI-mediated secretion. Protein levels for the tyrosine kinase Lyn are somewhat reduced but not absent in nonreleaser basophils, Levels of Lyn and Syk protein are similar in B cells,eosinophils, and neutrophils from releaser and nonreleaser donors. During these studies one nonreleaser "converted" into a releaser with concomitant basophil Syk expression. Conclusion: The absence of detectable Syk could explain the nonreleaser phenotype of basophils from some donors.