Introduction
IgE antibodies, also known as immunoglobulin E antibodies, play a crucial role in the immune system's response to allergens. When a person is exposed to an allergen, the body produces IgE antibodies that bind to the allergen and trigger a cascade of immune reactions that lead to various symptoms. These symptoms can include dermatological diseases such as eczema, hives, and allergic contact dermatitis. Understanding the role of IgE antibodies in the production of dermatological diseases is essential for developing effective treatments and managing these conditions. This article will explore the role of IgE antibodies in the production of dermatological diseases and how they contribute to the development of these conditions.
Which Dermatological Diseases Have Involvement of IgE Antibodies?
Dermatological diseases are a group of conditions that affect the skin, hair, and nails. These diseases can range from mild, such as a rash or hives, to severe, such as eczema or psoriasis. IgE antibodies are involved in the production of several dermatological diseases, including atopic dermatitis, urticaria, and angioedema.
-
Atopic dermatitis, also known as eczema, is a chronic skin condition that causes dry, itchy, and inflamed skin. The exact cause of atopic dermatitis is unknown, but it is thought to be related to a combination of genetic and environmental factors. IgE antibodies are involved in the development of atopic dermatitis, as they bind to allergens in the environment and trigger the release of inflammatory chemicals, leading to the characteristic symptoms of the disease.
-
Urticaria, also known as hives, is a common skin condition characterized by raised, itchy, and often red welts on the skin. Urticaria can be caused by a variety of factors, including allergies, infections, and medications. IgE antibodies are involved in the production of allergic urticaria, which is caused by an allergic reaction to an allergen. In this case, IgE antibodies bind to the allergen, triggering the release of histamine and other inflammatory chemicals, leading to the characteristic symptoms of urticaria.
-
Angioedema is a condition characterized by swelling in the deeper layers of the skin, often around the eyes and lips. It can be caused by a variety of factors, including allergies, medications, and genetic factors. IgE antibodies are involved in the production of allergic angioedema, which is caused by an allergic reaction to an allergen. In this case, IgE antibodies bind to the allergen, triggering the release of histamine and other inflammatory chemicals, leading to the characteristic symptoms of angioedema.
What Is the Role of IgE in the Pathophysiology of Dermatological Disease?
IgE plays a significant role in allergen-related inflammatory processes in several atopic dermatologic diseases. Immunoglobulin E binds to various immune cells through high-affinity IgE receptors. This can take place in the presence or absence of a beta chain. IgE acts as both an effector for the release of chemical mediators and a regulator for cytokine production. The mast cells and basophils receive signals for the release of preformed inflammatory mediators. However, Langerhans cells and inflammatory dendritic epidermal cells use the receptor for IgE-mediated internalization of antigens for antigen presentation.
Atopic dermatitis can be dichotomized into the following two forms:
-
Extrinsic Form: The extrinsic form constitutes around 80 percent of all children with atopic dermatitis and is driven by sensitization, skin barrier function abnormalities, and high-to-extremely high levels of IgE (more than or equal to 20,000 international units per milliliter).
-
Intrinsic Forms: Intrinsic atopic dermatitis presents with normal serum levels of total and specific IgE, a female predominance, and a relatively preserved skin barrier function.
More recently, based on the onset of the disease, four phenotypes of atopic disease are associated with or without food. Patients with an early onset of the disease and symptoms are more likely to present with more severe disease and a strong association with asthma and food allergies. Usually atopic disease is most commonly seen in young children and is resolved before adulthood. However, the presence of severe atopic disease with multiple factors such as the early onset of disease, food allergies, filaggrin gene mutations, and sensitization can lead to the persistence of the condition into adulthood. About 50 percent of the patients suffer from other allergic symptoms within the first year of life, and around 60 percent of children are affected with dermatological disease or other atopic co-morbidities.
What Is Anti-IgE Therapy in Dermatological Disease?
The therapeutic strategy behind the use of Omalizumab is blocking IgE and, subsequently, the mast cell and basophil activation in case of an allergic reaction. Omalizumab is the only anti-IgE antibody available and has been used for over 15 years of clinical experience, and over 1.3 million patients have been exposed to this medication.
The only available approved anti-IgE therapy for clinical use include Omalizumab. Various studies have been performed demonstrating the role of IgE and the efficacy of Omalizumab for the treatment of various dermatological diseases. Omalizumab is a monoclonal humanized anti-IgE antibody that can be used for the treatment of chronic spontaneous urticaria, severe allergic asthma, and chronic rhinosinusitis with nasal polyps.
Omalizumab acts by forming complexes with IgE and by binding to its Cε3 domain. The binding action of Omalizumab with free IgE reduces serum levels, resulting in an anti-inflammatory effect. Omalizumab-IgE complexes can capture any free antigen that can further trigger an immune response.
Omalizumab has been identified as a therapeutic option in various IgE-mediated allergic diseases such as food allergy, allergic asthma, and allergic rhinitis, as well as non-allergic diseases such as chronic rhinosinusitis with nasal polyps. Atopic treatment is an actively explored disease area for IgE-targeted treatment. Besides anti-IgE therapy using Omalizumab, plasma apheresis has also been explored as an innovative therapeutic option targeting IgE in patients.
Since Omalizumab has been used for over 15 years, its safety profile is well established. However, no dedicated Phase III study on the effect of Omalizumab on IgE has been conducted in patients with a dermatological disease like an atopic disease. Dedicated Phase II and III studies with an appropriate atopic disease population and robust design are still required. The study must effectively compensate for a high placebo effect to systematically investigate Omalizumab as a potential therapy for atopic disease and the role of IgE in the disease.
Conclusion:
It has been proved that IgE plays a significant role in the pathogenesis of dermatological diseases like atopic dermatitis. Drugs targeting IgE are considered an effective treatment option for many patients with atopic dermatitis.
Numerous studies have shown to demonstrate the benefits of Omalizumab treatment and IgE plasma apheresis. Since IgE is considered an epiphenomenon biomarker rather than a pathogenetic factor, certain studies suggest the use of Omalizumab has been inconclusive.
However, this concept is debatable considering that during these studies, a low dose of Omalizumab was used compared to the markedly elevated patient IgE levels, the small and heterogeneous populations studied, and the evidence that IgE seems to play an important role in most of the atopic disease patients with IgE targeting treatments proving its efficacy.
