Basic and clinical immunology
Effect of omalizumab treatment on peripheral eosinophil and T-lymphocyte function in patients with allergic asthma

https://doi.org/10.1016/j.jaci.2006.02.028Get rights and content

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-γ, or TNF-α 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.

Section snippets

Study design

Patients with moderate-to-severe allergic asthma participated in this study, which was conducted as part of a randomized, double-blind, placebo-controlled, parallel-group trial.20 All patients had a history of allergic asthma and allergic rhinitis with a positive skin prick test to a perennial allergen (Dermatophagoides farinae, Dermatophagoides pteronyssinus, cat or dog) and specific IgE (CAP; Pharmacia, Uppsala, Sweden). Patients had to have been receiving inhaled corticosteroids at doses

Patient characteristics

Nineteen patients were enrolled in the study (Table I). Baseline characteristics were well balanced between the treatment groups.

Eosinophils

Binding to Annexin V as marker of eosinophil apoptosis was significantly (P = .004) increased in the eosinophils of the omalizumab-treated group compared with placebo, whereas 7AAD was unchanged, indicating that cell death caused by necrosis was not important for this effect. Also, a significant (P = .0039) increase of Annexin-positive eosinophils was detectable

Discussion

This study shows that treatment with omalizumab leads to increased eosinophil apoptosis. Furthermore, we found a reduction in cellular production of GM-CSF, an important factor in eosinophil growth and survival.21 The fact that CD4 lymphocytes are the predominant subpopulation involved in this effect is important, because this population of lymphocytes orchestrates the late-phase allergic response that is accompanied by an influx of eosinophils. Furthermore, IL-2 and IL-13 producing lymphocytes

References (29)

  • S.S. Saini et al.

    Down-regulation of human basophil IgE and FCɛRIα surface densities and mediator release by anti-IgE-infusions is reversible in vitro and in vivo

    J Immunol

    (1999)
  • J.V. Fahy et al.

    The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects

    Am J Respir Crit Care Med

    (1997)
  • R. Buhl et al.

    Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma

    Eur Respir J

    (2002)
  • R. Buhl et al.

    The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma

    Eur Respir J

    (2002)
  • Cited by (176)

    • Unmet Needs in Severe Allergic Asthma

      2023, Open Respiratory Archives
    • T-cell responses in asthma exacerbations

      2022, Annals of Allergy, Asthma and Immunology
    View all citing articles on Scopus

    Supported by Novartis Pharma Germany.

    Disclosure of potential conflict of interest: O. Noga, G. Hanf, A. Klucken, S. Rosseau, G. Kunkel, N. Suttorp, and J. Seybold have all received a grant from Novartis Pharma. The rest of the authors have declared that they have no conflict of interest.

    View full text