Comparable actions of omalizumab on mast cells and basophils.
BACKGROUND
Omalizumab (OmAb) has recently been approved for the treatment of diseases other than allergic asthma, including chronic urticaria. The exploration of the use of OmAb in chronic urticaria was based on the presence of IgE autoantibodies against autoantigens such as anti-IgE, anti-FcεRI, and IgE antibodies against thyroid peroxidase in certain patients with chronic urticaria. OmAb recognizes and sequesters free IgE to prevent its interaction with FcεRI. However, OmAb is equally and rapidly effective against autoimmune and non-autoimmune urticaria, suggesting the possible involvement of additional mechanisms of IgE.


OBJECTIVE
We sought to investigate the in vitro mechanism of action of OmAb in mast cells and basophils.


METHODS
Both LAD2 human mast cell line, previously sensitized with IgE, and ex vivo basophils were incubated with OmAb at different doses, analysing its effect on IgE-dependent events (e.g., degranulation, phosphorylation-mediated signalling, and eicosanoid release).


RESULTS
We found that OmAb dissociates pre-bound IgE from mast cells and basophils, resulting in a reduction of proximal phosphorylation-mediated signalling events (Syk, PLCγ, and LAT) and in a decrease in degranulation and leukotriene synthesis.


CONCLUSIONS
Our data prove the existence of common mechanisms of action of OmAb in mast cells and basophils that would explain its effectiveness and rapid effect in chronic urticaria and provide a basis for its use in other diseases mediated by these cells.
Biochemistry Unit, Faculty of Medicine, University of Barcelona, Barcelona, Spain.|Laboratory of Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, Barcelona, Spain.
E
E
Serrano-Candelas
Department of Allergy and Clinical Immunology, Clinica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain.
R
R
Martinez-Aranguren
Laboratory of Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, Barcelona, Spain.|Department of Pneumology and Allergy, Immunoallèrgia Respiratòria Clínica I Experimental, IDIBAPS, Hospital Clínic, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
A
A
Valero
Laboratory of Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, Barcelona, Spain.|Department of Pneumology and Allergy, Immunoallèrgia Respiratòria Clínica I Experimental, IDIBAPS, Hospital Clínic, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
J
J
Bartra
Department of Allergy and Clinical Immunology, Clinica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain.
G
G
Gastaminza
Department of Allergy and Clinical Immunology, Clinica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain.
M J
MJ
Goikoetxea
Biochemistry Unit, Faculty of Medicine, University of Barcelona, Barcelona, Spain.|Laboratory of Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, Barcelona, Spain.
M
M
Martín
Department of Allergy and Clinical Immunology, Clinica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain.
M
M
Ferrer
D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001491:Basophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000069444:Omalizumab / Q000494:pharmacology*; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism
D018926:Anti-Allergic Agents; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; D000069444:Omalizumab; D007073:Immunoglobulin E
FcεRI; IgE; basophils; chronic urticaria; mast cells; omalizumab