Effect of omalizumab treatment on peripheral eosinophil and T-lymphocyte function in patients with allergic asthma.
Author(s): Noga O, Hanf G, Brachmann I, Klucken AC, Kleine-Tebbe J, Rosseau S, Kunkel G, Suttorp N, Seybold J
Affiliation(s): Department of Internal Medicine, Charite Universitatsmedizin Berlin, Germany. firstname.lastname@example.org
Publication date & source: 2006-06, J Allergy Clin Immunol., 117(6):1493-9. Epub 2006 Apr 27.
Publication type: Randomized Controlled Trial
BACKGROUND: Omalizumab is a recombinant monoclonal anti-IgE antibody with proven efficacy in allergic diseases and further anti-inflammatory potency in the treatment of asthma. OBJECTIVES: To explore the anti-inflammatory mechanism of omalizumab, we investigated the induction of immunologic changes leading to eosinophil apoptosis and examined T-lymphocyte cytokine profiles in patients with allergic asthma. METHODS: Nineteen patients with allergic asthma were enrolled and received omalizumab at a dose of at least 0.016 mg/kg/IgE (IU/mL) every 4 weeks. Peripheral eosinophils and T-lymphocyte cytokine profiles were evaluated by fluorescence-activated cell sorting before treatment (baseline), at 12 weeks of treatment, and 12 weeks after discontinuation of treatment with omalizumab or placebo. RESULTS: Markers of eosinophil apoptosis (Annexin V) were significantly increased in omalizumab recipients compared with placebo, whereas no changes in markers of necrosis (7-amino-actinomycin) or eosinophil activation CD69 or Fas receptor (CD95) were detected. GM-CSF+ lymphocytes were reduced in omalizumab recipients compared with placebo. Fewer IL-2+ and IL-13+ lymphocytes were evident in omalizumab recipients than in the placebo group. There were no significant differences in IL-5, IFN-gamma, or TNF-alpha between the omalizumab and placebo groups. CONCLUSION: These findings provide further evidence that omalizumab has additional anti-inflammatory activity demonstrated by induction of eosinophil apoptosis and downregulation of the inflammatory cytokines IL-2 and IL-13. Further studies are needed to determine the underlying mechanisms. CLINICAL IMPLICATIONS: These findings support the critical role of IgE in the regulation of inflammation in allergic asthma: influencing the inflammation is the key to control the more severe type of asthma.