Auto-antibodies to IgE and FceRI and the Natural Variability of SYK Expression in Basophils

Publication date: Available online 1 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Donald MacGlashan
BackgroundSecretion from human basophils and mast cells requires the activity of SYK but expression of SYK is highly variable in the general population and this variability predicts the magnitude of IgE-mediated secretion. One known mechanism of modulating SYK expression in human basophils is aggregation of FceRI.ObjectiveThis study examines the possibility that functional auto-antibodies are present in a wide variety of subjects and in particular, subjects whose basophils poorly express SYK. It also tests whether any found antibodies could modulate SYK expression in maturing basophils and whether interaction with FcgRIIb/CD32b modulates the effect.MethodsAn experimental algorithm for classifying the nature of histamine release induced by serum from 3 classes of subjects was developed.ResultsThe frequency of functional auto-antibodies that produce characteristics concordant with FceRI-mediated secretion was zero in 34 subjects without chronic spontaneous urticaria (CSU). In subjects with CSU, the frequency was lower than expected, approximately 7%. For the 5/68 unique CSU sera tested that contained anti-FceRI or anti-IgE Abs, these antibodies were found to induce down-regulation of SYK in both peripheral blood basophils and basophils developed from CD34+ progenitors. Blocking interaction of these antibodies with CD32b did not alter their ability to down-regulate SYK expression.ConclusionsThis study establishes that functional auto-antibodies to IgE/FceRI do not provide a good explanation for the variability in SYK expression in basophils in the general population. They do show that if antibodies with these characteristics are present, they are capable of modulating SYK expression in developing basophils.

Teaser

The wide variability in the critical signaling tyrosine kinase SYK observed in the general population is not explained by the presence of auto-antibodies to IgE or FceRIalpha.


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