Regulation of Syk kinase and FcRbeta expression in human basophils during treatment with omalizumab.
BACKGROUND
In human basophils from different subjects, maximum IgE-mediated histamine release and the level of Syk protein expression correlate well. Recent studies suggest that in some patients treated with omalizumab, the response to stimulation with anti-IgE antibody increases. In unrelated studies there is also evidence that the composition of FcepsilonRI in basophils differs among subjects. This observation raised the possibility that the stoichiometry of FcRbeta/FcepsilonRIalpha is not fixed to a 1:1 ratio and might be modifiable during changes in the basophil's environment.


OBJECTIVE
We sought to determine whether treatment with omalizumab results in increases in Syk expression and anti-IgE-mediated histamine release and disproportionately alters the relative presence of FcRbeta and FcepsilonRIalpha.


METHODS
Syk, FcepsilonRIalpha, and FcRbeta expression was monitored during the treatment of subjects with omalizumab.


RESULTS
Treatment with omalizumab reduced histamine release from peripheral blood leukocytes stimulated with cat allergen in vitro, but histamine release stimulated with anti-IgE antibody increased 2-fold. Expression of Syk increased 1.86-fold. There was no change in the expression of c-Cbl, a signaling element that is sensitive to the presence of IL-3, and no increase in response to formyl-met-leu-phe (tripeptide), a response that also increases in the presence of IL-3. There was a 60% decrease in the FcRbeta/FcepsilonRIalpha ratio in patients treated with omalizumab.


CONCLUSIONS
In the context of previous studies, these studies provide support for a proposal that Syk expression is modulated in vivo through an IgE-dependent mechanism and that the ratio of FcepsilonRI alpha and beta subunits in basophils is influenced by factors extrinsic to the cell.
Zaidi
Asifa K
AK
Johns Hopkins Asthma and Allergy Center, Baltimore, Md, USA.
Saini
Sarbjit S
SS
Macglashan
Donald W
DW
D000293:Adolescent; D000328:Adult; D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001491:Basophils / Q000276:immunology*; D002415:Cats; D005786:Gene Expression Regulation; D006636:Histamine Release; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008875:Middle Aged; D000069444:Omalizumab; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D016896:Treatment Outcome; D055815:Young Adult
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D000069444:Omalizumab; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase