dIvergEnt: How IgE Axis Contributes to the Continuum of Allergic Asthma and Anti-IgE Therapies

Abstract

Asthma is an airway disease characterised by chronic inflammation with intermittent or permanent symptoms including wheezing, shortness of breath, chest tightness, and cough, which vary in terms of their occurrence, frequency, and intensity. The most common associated feature in the airways of patients with asthma is airway inflammation. In recent decades, efforts have been made to characterise the heterogeneous clinical nature of asthma. The interest in improving the definitions of asthma phenotypes and endotypes is growing, although these classifications do not always correlate with prognosis nor are always appropriate therapeutic approaches. Attempts have been made to identify the most relevant molecular and cellular biomarkers underlying the immunopathophysiological mechanisms of the disease. For almost 50 years, immunoglobulin E (IgE) has been identified as a central factor in allergic asthma, due to its allergen-specific nature. Many of the mechanisms of the inflammatory cascade underlying allergic asthma have already been elucidated, and IgE has been shown to play a fundamental role in the triggering, development, and chronicity of the inflammatory responses within the disease. Blocking IgE with monoclonal antibodies such as omalizumab have demonstrated their efficacy, effectiveness, and safety in treating allergic asthma. A better understanding of the multiple contributions of IgE to the inflammatory continuum of asthma could contribute to the development of novel therapeutic strategies for the disease.

Keywords: allergy; anti-IgE; asthma; biological treatment; biomarkers; immunoglobulin E (IgE); immunological mechanisms; immunomodulation; omalizumab.

Figure 1

The Iceberg model of allergic asthma. Allergic asthma is characterised by a visible part of the disease; however, many pathophysiological changes of this complex process occur in the depths. Changes at the level of lymphatic nodes, peripheral blood, and submucosa appear from the beginning of the disease and should be addressed in order to minimise the impact and persistency of symptoms. The influence of IgE is present across all levels of the iceberg. Further details can be found in the text. ECP: eosinophil cationic protein, FcεRI: high affinity IgE receptor, FcεRII: low affinity IgE receptor, GM-CSF: granulocyte-macrophage colony-stimulating factor, IFNγ: interferon gamma, IgE: immunoglobulin E, IL: interleukin, ILC: innate lymphoid cells, LTC4: leukotriene C4, MBP: major basic protein, MCP: monocyte chemotactic protein, MRP: myeloid related proteins, PAF: platelet-activating factor, TGFβ: transforming growth factor beta, Th: T helper cells, TLR: toll-like receptors, TNFα: tumor necrosis factor alpha, Treg: regulatory T cells, TSLP: thymic stromal lymphopoietin.

Figure 2

A continuum scenario in the immunoglobulin E (IgE) role in allergic asthma. The IgE has a central role in the continuum cascade of allergic reaction and participates in all phases: the sensitivity phase reaction, the early clinical phase, the late clinical phase, and the final chronic consequences. ILC2: type 2 innate lymphoid cells, Th: T helper cells, Treg: regulatory T cells.