Immunologic Basis of Anti-IgE Therapy (Study II: On Patients With Asthma)
Condition: Asthma; Allergic Rhinitis; Atopic Dermatitis
MeSH terms: Rhinitis; Asthma; Rhinitis, Allergic; Dermatitis
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to look at measures that will help scientists understand the way
      Omalizumab, an FDA-approved anti-allergy medication, works.
    

Detailed description: 
      IgE is a key molecule involved in immediate hypersensitivity and plays a major role in the
      pathogenesis of allergic diseases. Recently, a therapy based on the use of anti-IgE antibody
      has been developed by a pharmaceutical company, Genentech. A number of clinical trials have
      demonstrated that these antibodies are efficacious in treatment of allergies, including
      allergic rhinitis and asthma. The medication Omalizumab (Xolair) has recently been approved
      by the FDA for treatment of asthma.

      The mechanism underlying the beneficial effect of this therapy is not completely understood,
      but is likely to be related to the marked reduction in the IgE level. Of note is the
      concomitant accumulation of IgE-anti-IgE complexes in the sera. Another remarkable effect of
      the treatment is the substantial reduction in the FcεRI level on basophils, which is likely a
      key factor contributing to the therapeutic benefit of the drug. The existing literature
      suggests that the reduction in the IgE level is likely to result in a down-regulation of
      another IgE receptor, FcεRII/CD23. Because of the known immunomodulatory function of FcεRII,
      anti-IgE therapy may result in alterations of the immune system, in addition to simple
      absorption of IgE.

      We propose to conduct mechanistic studies of anti-IgE therapy. The objectives are to address
      how anti-IgE therapy works and how it might affect the immune system in general. The proposed
      studies also take advantage of this well-defined therapy to address some basic questions
      regarding the immune system. Our hypothesis is that anti-IgE therapy may have general effects
      on the immune system, such as reduced IgE-mediated antigen presentation by antigen-presenting
      cells and suppressed allergen-specific IgE and IgG production. The specific aims of the
      proposed research are:

        1. Determination of the effect of anti-IgE therapy on FcεRI expression and basophil
           responses. We will first confirm that anti-IgE therapy causes a reduction in the FcεRI
           level on basophils and then analyze whether this occurs at a transcriptional level. We
           will confirm that the therapy causes a reduction in basophil response to cross-linkage
           of FcεRI and then determine whether it also affects basophil response induced by non-IgE
           stimuli. The effect of the therapy on the FcεRI level on skin mast cells will also be
           investigated.

        2. Determination of the effect of anti-IgE therapy on FcεRII expression and antigen
           presentation. We will determine whether the therapy results in a down-regulation of
           FcεRII/CD23 on B cells. Because of the demonstrated function of FcεRII/CD23 in antigen
           presentation, we will determine the antigen presentation to T cells by B cells from
           anti-IgE-treated and control subjects.

        3. Determination of the effect of anti-IgE therapy on antibody production. We will
           determine whether anti-IgE therapy results in a suppression of IgE production, in
           addition to sequestration of IgE. Whether IgE-anti-IgE complexes directly suppress IgE
           production by B cells in vitro will be investigated.
    

Intervention name(s): Omalizumab; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Xolair (Omalizumab) will be given by subcutaneous injection according to Ige level and weight calculation.; Placebo, given by subcutaneous injection.
Other intervention name(s): Xolair
Intervention MeSH terms: Omalizumab
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment