Reduced FcepsilonRI-mediated release of asthma-promoting cytokines and chemokines from human basophils during omalizumab therapy.
BACKGROUND
Treating asthmatics with the humanized IgE-scavenging antibody, omalizumab (rhuMAb-E25, Xolair, reduces airways inflammation and asthma symptoms. Previously, omalizumab was shown to cause a dramatic and reversible loss of cell surface high-affinity IgE receptors, FcepsilonRI, from the peripheral blood basophils of asthmatics. The consequences of receptor loss for the FcepsilonRI-mediated synthesis and release of cytokines implicated in allergic asthma have not been examined.


METHODS
Fifteen asthmatic volunteers each received omalizumab for 12 weeks. Peripheral blood basophils were isolated before, during, 2 weeks after and 6 months after omalizumab. Basophils were assayed for the basal and anti-IgE-stimulated release of cytokines, chemokines and histamine. Pooled data were analyzed by repeated measures ANOVA and by paired t tests.


RESULTS
Anti-IgE-stimulated human basophils synthesize and release Th2 cytokines (IL-4, IL-13) and chemokines (IL-8, RANTES). The anti-IgE-stimulated release of IL-4, IL-13 and IL-8 was reduced during omalizumab treatment and returned to pretreatment levels after omalizumab withdrawal. Omalizumab did not alter basophil histamine levels or basal and anti-IgE-stimulated histamine release.


CONCLUSIONS
Omalizumab may reduce asthma symptoms in part by suppressing the FcepsilonRI-mediated production by basophils of Th2 cytokines and selected chemokines. Anti-IgE-stimulated basophil cytokine synthesis appears more sensitive than histamine release to the loss of FcepsilonRI caused by omalizumab treatment.
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. joliver@salud.unm.edu
Janet M
JM
Oliver
Christy A
CA
Tarleton
Laura
L
Gilmartin
Tereassa
T
Archibeque
Clifford R
CR
Qualls
Lorena
L
Diehl
Bridget S
BS
Wilson
Mark
M
Schuyler
D000293:Adolescent; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D001491:Basophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069444:Omalizumab; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; C543355:FcepsilonRI alpha-chain, human; D017455:Receptors, IgE; D000069444:Omalizumab