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Anti-IgE-Based Therapy Development

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Introduction of IgE

IgE is the immunoglobulin responsible for the initiation of type I hypersensitivity reactions, such as those in the primary allergic diseases of asthma, allergic rhinitis, and food allergy. Allergic disorders, including asthma, allergic rhinoconjunctivitis, and food allergy, represent significant health and socioeconomic burden. An increased prevalence of allergic diseases worldwide has heralded a renewed interest in research in the prevention and treatment of asthma and allergic rhinitis. Although therapeutic modalities such as antihistamines, inhaled steroids, and antileukotrienes demonstrate some effectiveness in ameliorating allergy symptoms, a significant number of patients with allergies still experience daily discomfort. Therapies that more effectively block the effects of IgE hold promise for preventing symptoms caused by allergic reactions.

Mechanism of IgE-Based Therapy

In genetically predisposed individuals, the inhalation of allergens (such as animal dander, grass, or weed pollens) stimulates a unique immunologic response, ending in the production of allergen-specific IgE by B cells and plasma cells. Once released, free IgE enters the bloodstream, where it binds to mast cells and basophils by means of high-affinity cell surface receptors (FceRI). Basophil and mast cell degranulation occurs when specific allergen molecules of the appropriate size and configuration form cross-link between the Fab portions of two adjacent IgE molecules on the cell surface. Such degranulation results in the release of mediators (histamine, prostaglandins, leukotrienes) and cytokines (interleukin 4 [IL-4], IL-5, IL-13) that bring about the pathophysiologic consequences and symptoms of allergic diseases, such as asthma, rhinitis, and food allergy.

The allergic cascade. Fig.1 The allergic cascade. (Brownell, 2004)

Epidemiologic studies have confirmed the importance of IgE in allergic respiratory disorders. The prevalence of asthma has been correlated with increased levels of serum IgE, and serum IgE levels have been linked to persistent wheezing in children. These levels also have been shown to predict human airway reactivity in vitro. Epidemiologic and basic research studies have confirmed a clear relationship between IgE and the pathogenesis and development of symptoms associated with allergic respiratory diseases.

IgE-Based Therapy

The anti-IgE antibody specifically binds circulating free IgE at the high-affinity receptor binding site, thus inhibiting the binding of the antibody to effector cells. Once bound to free IgE, small complexes are formed. IgE complexes are trimers of approximately 490-530 kD or hexamers of approximately 1,000 kD. The size of complexes depends on the relative concentrations of both serum-free IgE and anti-IgE antibodies. The anti-IgE antibody does not cause cross-linking of the IgE receptor or subsequent effector cell degranulation, a property that has been referred to as its being nonanaphylactogenic.

Mechanisms of action of anti-IgE antibody. Fig.2 Mechanisms of action of anti-IgE antibody. (Bayar Muluk, 2019)

The anti-IgE antibody has been proved to be useful in the therapy of allergic respiratory disorders. It reduces levels of serum IgE and FceRI receptors as its primary mechanisms of action. It has been shown to improve asthma in adults, adolescents, and children, allowing a reduction in steroid doses. It also improves symptoms, rates of urgent care visits, rescue medication use, and quality of life. In these studies, anti-IgE antibodies seemed to be safe and well-tolerated. It has been approved for the therapy of adults and adolescents with moderate-to-severe allergic asthma who have persistent symptoms despite therapy, intolerable side effects from therapy, or poor compliance. Patients with asthma who have concomitant IgE-mediated disorders, such as allergic rhinitis and food allergy, are likely to benefit from this drug, but further studies are necessary before such recommendations can be made.

Services at Creative Biolabs

Anti-IgE-based therapy has been a long time focused because of its important role in allergies. It is also an important role in non-IgG antibodies' applications. Creative Biolabs has a comprehensive technology platform professional at non-IgG antibodies research. Services our platform offers include but are not limited to:

If you are interested in non-IgG antibodies-relevant services or you have any other questions, please don't hesitate to contact us for more information.

References

  1. Brownell, J. and Casale, T. B. Anti-IgE therapy. Immunol Allergy Clin North Am. 2004, 24(4): 551-68, v.
  2. Bayar Muluk, N.; et al. Anti-IgE treatment in allergic rhinitis. Int J Pediatr Otorhinolaryngol. 2019, 127: 109674.

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