• J Gericke, T Ohanyan, M K Church, M Maurer, and M Metz.
• Department of Dermatology, Venerology and Allergology, Allergie-Centrum-Charité, Charité-Universitätsmedizin, Berlin, Germany.
• J Eur Acad Dermatol Venereol. 2015 Sep 1; 29 (9): 1832-6.

BackgroundIn March 2014, omalizumab, a monoclonal anti-IgE antibody, was approved for the treatment of chronic spontaneous urticaria (CSU). The primary mode of action of omalizumab is considered to be the reduction in free IgE serum levels and the subsequent down-regulation of FcεRI, the high affinity receptor for IgE, on mast cells and basophils. Recently, it has been suggested that most CSU patients have an autoimmune aetiology which may lead to chronic activation of mast cells and basophils.ObjectiveTo understand more of the mechanisms by which omalizumab may exert its effects in CSU, its efficacy was tested on human mast cells and basophils.MethodsOmalizumab, which was or was not preincubated with serum from healthy donors or CSU patients, was coincubated with isolated healthy donor skin mast cells or peripheral blood-derived monocytes containing 1-2% basophils. Degranulation was induced using anti-human IgE, C5a, or substance P and histamine release determined.ResultsAnti-human IgE-induced histamine release from mast cells or basophils was not altered in the presence or absence of omalizumab. In contrast, preincubation of mast cells with DARPin Fc fusion protein, a positive control for negative signalling via FcεRI-FcγRIIb cross activation, significantly diminished histamine release. Moreover, omalizumab, that was preincubated with healthy donor serum, CSU patient serum or auto-reactive CSU serum to allow for the formation of potential immune complexes, did not alter induced histamine release in a coincubation setup with mast cells or basophils as compared to the absence of omalizumab. In vivo, blood basophil numbers and basophil histamine content increase under omalizumab therapy.ConclusionOur results suggest that the rapid response to omalizumab therapy is more likely to result from the elimination of an activating signal rather than the generation of a negative, inhibitory signal.© 2014 European Academy of Dermatology and Venereology.

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