Back To Search Results

Biochemistry, Immunoglobulin E

Editor: Jonathan S. Crane Updated: 9/24/2022 7:56:51 AM


Immunoglobulin E is one of the five classes of immunoglobulins (IgM, IgG, IgD, IgA, IgE). IgE has a unique chemical structure and an array of physiological functions, such as Type I hypersensitivity reactions, parasitic infections, autoimmune processes, and venom protection.[1]It was the last of the immunoglobulin family to be discovered, and since then has spurred vast amounts of research aimed at characterizing its biochemistry and role in disease processes. There have also been advancements in technology used to evaluate patient IgE levels and new pharmacological therapies that may inhibit its function altogether.[2] The following article aims to provide an overview detailing the biochemical structure and function of Immunoglobulin E, as well as some examples of its clinical implications.

Molecular Level

Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Molecular Level

All immunoglobulin molecules have a common structural framework characterized by two identical small polypeptide chains (light chains) and two identical large polypeptide chains (heavy chains). The Fc region of the antibody is comprised solely of the two heavy chains and is responsible for binding to cellular receptors. The Fab region of the antibody is where antigen recognition and binding occur and is made up of two heavy chains continuous with the Fc region and two light chains. These chains also have variable and constant regions. At the antigen binding sites, both polypeptide chains contain variable regions whose amino acid sequences can be altered for affinity maturation to occur for a given antigen. The variable heavy and light chains are organized into layers of antiparallel B-pleated sheets, allowing the antigen to bind between these three-dimensional immunoglobulin folds. The rest of the polypeptide regions are known as constant regions, and they are held together by strong dipeptide bonds to stabilize the two chains.[3]

Some antibodies, like IgM, can have five duplicates of the structure above to form a pentamer capable of binding up to ten antigens. However, IgE is a monomer composed of two epsilon-heavy chains and two light chains, thus capable of binding a total of two antigens, which occurs through the variable regions of the light and heavy chains that create unique antigen-specific binding sites. The C-terminal regions of the heavy chains are composed of four C-epsilon dimers, C-epsilon 1-4.[4] The chemical structure of these dimers is essential for binding IgE-specific cellular receptors Fc-epsilon R1 and CD23, which will be discussed in more detail later. Some immunoglobulins, such as IgG, contain a "hinge" region near the molecule's center. IgE is unique because it lacks this hinge region and is replaced by the C-epsilon2 domain. There is a theory that the lack of this hinge region allows the IgE molecule to adopt a more flexible conformation while interacting with its receptors. Furthermore, the IgE molecule is more heavily glycosylated than other antibodies, containing 7 N-linked glycosylations on each heavy chain, which is necessary for binding to a high-affinity cellular receptor, Fc-epsilon-R1.[4] 


The biochemical considerations mentioned determine the structure of IgE and drive the function of allowing IgE to bind to given antigens and IgE-specific cellular receptors. For Immunoglobulin E to accomplish its function, the Fc portion of the antibody must bind to a given cellular receptor located on a particular type of cell, such as a mast cell, eosinophil, etc. Although many cellular receptors have been identified and studied, the main ones are Fc-epsilon-RI and Fc-epsilon-RII, or CD23. [5] Fc-epsilon-RI, or the high-affinity receptor, is mainly located on mast cells, basophils, dendritic cells, macrophages, and eosinophils. It is thus responsible for immediate hypersensitivity reactions, parasitic immunity, enhanced cytokine production, and antigen presentation. The other receptor, CD23, or the low-affinity receptor, is primarily expressed on B-cells, T-cells, and antigen-presenting cells (APCs) and is responsible for IgE production homeostasis, facilitated antigen presentation (FAP), as well as transportation of IgE across airway and gut epithelia.[6]


The role of Immunoglobulin E is central in allergy sensitization and atopic disorders such as allergic rhinitis, asthma, and atopic dermatitis. These disorders manifest due to Type I hypersensitivity reactions involving IgE and other immune cells to produce the clinical symptoms seen in those disorders ultimately. It starts with an initial exposure to an antigen or allergen, which is taken up and processed by a dendritic cell or macrophage, which presents the antigen to a T cell. In the presence of cytokine mediators IL-4 and IL-13, these T cells are induced to differentiate into TH2 helper T cells capable of presenting the antigen to B-cells.[6] The B-cells then undergo class-switching recombination events to produce Immunoglobulin E antibodies capable of binding to the presented antigen at the “antigen binding site” of the Fab portion of the antibody. Once this initial sensitization to antigen has occurred, more immunological events can ensure a more robust IgE response. The CD23 receptor on intestinal or airway epithelial cells can transport antigen-IgE complexes across the epithelium to bind Fc-epsilon-RI receptors on mast cells, macrophages, and other immune cells to promote inflammation, cytokine production, and more local IgE production. Furthermore, via interaction with the CD23 receptor on B-cells and myeloid cells, a process known as facilitated antigen presentation (FAP) can occur. FAP involves antigen-IgE complexes binding to CD23 receptors on B-cells, which then present the peptides to T-cells to facilitate further IgE antibody production. [7] This approach contrasts with the classical antigen presentation pathway described above. Instead of T-cells being the primary antigen presenters to the B-cell, it is now antigen-IgE complexes formed in the periphery, which may or may not be related to the initial antigen. This has clinical importance because, via facilitated antigen presentation, the B-cells will ultimately present a diverse array of peptides to T-cells to clear it for further immunoglobulin production. In conclusion, this is a mechanism for epitope spreading, where an antibody response for one antigen can cause the production of antibodies to different antigens.[6] This could be why individuals can develop allergies to multiple antigens resulting in a phenomenon known as ‘atopic march.’[8] For example, a child could have atopic dermatitis and later in life develop asthma. In conclusion, facilitated antigen presentation produces a more robust immune response to a given antigenic exposure that could be responsible for sensitization to multiple unrelated antigens. 

Once initial exposure to an antigen has occurred, and an immune response has been activated, antigen-specific IgE will remain bound via the Fc-epsilon RI receptor to mast cells and basophils. It has been shown that binding alone of IgE to that receptor cause IgE-dependent upregulation of mast cell Fc-epsilon RI receptor expression, which allows these cells to bind more IgE antibodies.[6] Furthermore, it is essential to note that IgE has a short half-life in plasma, usually less than a day. However, IgE bound to a high-affinity receptor (Fc-epsilon RI) can remain attached to mast cells in tissues for weeks to months.[4] Later, upon re-exposure to a given antigen, crosslinking of adjacent Fc-epsilon RI-bound IgE antibodies occurs and binds the antigen, which causes subsequent aggregation of Fc-epsilon RI receptors. Once this happens and there is a sufficient aggregation of these receptors with bound antigen, it causes mast cells and basophils to release preformed chemical mediators stored in cytoplasmic granules such as histamine, serotonin, tryptase, prostaglandins, leukotrienes, and eosinophil/neutrophil chemotactic factors.[6]

Clinical Significance

It is essential to note that not everyone exposed to environmental antigens will generate a strong immune reaction described above. Certain people, known as ‘atopics,’ have a genetic predisposition for developing type one hypersensitivity responses to antigens in the environment. Clinically, the manifestations of this type one hypersensitivity reaction are usually due to the actions of the released chemical mediators such as histamine, leukotrienes, and other cytokines. Histamine release causes increased vascular permeability, smooth muscle constriction, and mucus secretion. Leukotrienes B4, C4, D4, and E4 are also often secreted and responsible for chemotaxis, inflammation, and anaphylaxis. Furthermore, if in enough quantity, histamine and other mediators can cause systemic vascular effects such as vasodilation and increased vessel permeability, causing hypotension and edema.[6] This could lead to anaphylactic shock and death if severe and poorly managed. 

The manifestations can occur in many different areas of the body. Involvement of the upper airway can cause many patients to suffer from mild seasonal allergies or allergic rhinitis. Due to repeated inhalation exposure to pollen and other outdoor antigens, type one hypersensitivity occurs, and mast cell degranulation causes epiphora, rhinorrhea, cough, and other symptoms. Additionally, the involvement of the lower airway in patients with atopic asthma experiences an immune response to aeroallergens resulting in airway smooth muscle constriction, increased mucus production and inflammation that manifests as obstructive lung disease. The skin can often be involved, and due to vasodilation and dermal edema, urticaria or ‘wheals’ can be evident.[9] Another skin disease that has been studied concerning the roles of IgE and hypersensitivity is atopic dermatitis or eczema. Although eczema is a multifactorial disease involving genetics, barrier dysfunction, and immune dysregulation, some evidence suggests IgE-mediated hypersensitivity may also play a role.[10] The inflammatory infiltrates of AE lesions are composed mainly of CD4+ helper T cells, with a predominance of TH2 cells, which are responsible for initiating IgE class switching by B cells. Certain aeroallergens were found to penetrate compromised skin in eczema patients and interact with Langerhans cells. Furthermore, these same cells were discovered to have IgE binding structures on their surface.[11] A correlation has also revealed that up to 80 to 85 percent of patients with atopic dermatitis have elevated IgE levels.[12] One study even conducted atopy patch tests on eczema patients and correlated their allergen-specific serum IgE. It showed that most patients (40%, N=151) with positive atopy patch test for D. pteronyssinus (house dust allergen) also had elevated serum IgE specific for that antigen. This study also demonstrated that there were patients (9%) with a positive atopy patch test and no elevation in serum IgE, in addition to other patients with a negative patch test.[11] Thus, given the known multifactorial nature of atopic dermatitis, it is likely that some correlation may exist between IgE-mediated hypersensitivity and eczema. However, the exact nature of this relationship requires further investigation.

Immunoglobulin E has also been implicated in the defense against parasitic organisms such as helminths. Helminthic infections are usually the result of soil transmission and infect up to one-third of people worldwide.[13] When the immune system encounters this type of parasite, the B-cell class switch to IgE antibodies, which then ‘coat’ the parasite via binding many antibodies. Following this, effector cells such as eosinophils and mast cells recognize Immunoglobulin E bound to the helminth and can then attach the Fc portion of the antibody via the Fc-epsilon RI receptor. Once connected, subsequent reactions occur, such as further cytokine release and histamine production by mast cells, as well as major essential protein and eosinophil peroxidase production by eosinophils.[14] These substances are toxic to the helminth and can thus result in parasitic killing and the ultimate clearance of the invader. 

As depicted in this article, Immunoglobulin E has a specific biochemical structure and function that guides its unique role in disease processes such as Type I hypersensitivity reactions, helminthic infections, and more. The research in the past 50 years regarding IgE has established a better idea of its role in disease. Not only has this aided in a more in-depth clinical understanding of IgE-related health disorders, but it has even spurred novel treatment modalities. A humanized monoclonal antibody named omalizumab has been engineered, which targets the IgE antibody, thus rendering it ineffective in producing associated symptoms. This drug has been shown to provide benefits and relief in patients with moderate to severe asthma and intermittent and persistent allergic rhinitis.[15] Despite this progress, much more remains to be learned about the exact function of this immunoglobulin in those diseases in which some correlation has already been established, as well as novel clinical relationships yet to be discovered. 


(Click Image to Enlarge)
Schematic diagram of the basic unit of immunoglobulin (antibody)
Schematic diagram of the basic unit of immunoglobulin (antibody) 1. Fab 2. Fc 3. heavy chain (consist of VH, CH1, hinge, CH2 and CH3 regions: from N-term) 4. light chain (consist of VL and CL regions: from N-term) 5. antigen binding site 6. hinge regions
Contributed by Y_Tambe (via Wikimedia through CC By-SA 3.0



Sutton BJ, Davies AM, Bax HJ, Karagiannis SN. IgE Antibodies: From Structure to Function and Clinical Translation. Antibodies (Basel, Switzerland). 2019 Feb 22:8(1):. doi: 10.3390/antib8010019. Epub 2019 Feb 22     [PubMed PMID: 31544825]


Ansotegui IJ,Melioli G,Canonica GW,Caraballo L,Villa E,Ebisawa M,Passalacqua G,Savi E,Ebo D,Gómez RM,Luengo Sánchez O,Oppenheimer JJ,Jensen-Jarolim E,Fischer DA,Haahtela T,Antila M,Bousquet JJ,Cardona V,Chiang WC,Demoly PM,DuBuske LM,Ferrer Puga M,Gerth van Wijk R,González Díaz SN,Gonzalez-Estrada A,Jares E,Kalpaklioğlu AF,Kase Tanno L,Kowalski ML,Ledford DK,Monge Ortega OP,Morais Almeida M,Pfaar O,Poulsen LK,Pawankar R,Renz HE,Romano AG,Rosário Filho NA,Rosenwasser L,Sánchez Borges MA,Scala E,Senna GE,Sisul JC,Tang MLK,Thong BY,Valenta R,Wood RA,Zuberbier T, IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper. The World Allergy Organization journal. 2020 Feb     [PubMed PMID: 32128023]


Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. The Journal of allergy and clinical immunology. 2010 Feb:125(2 Suppl 2):S41-52. doi: 10.1016/j.jaci.2009.09.046. Epub     [PubMed PMID: 20176268]

Level 3 (low-level) evidence


Oettgen HC, Fifty years later: Emerging functions of IgE antibodies in host defense, immune regulation, and allergic diseases. The Journal of allergy and clinical immunology. 2016 Jun;     [PubMed PMID: 27263999]


Poole JA,Rosenwasser LJ, The role of immunoglobulin E and immune inflammation: implications in allergic rhinitis. Current allergy and asthma reports. 2005 May     [PubMed PMID: 15842964]


Galli SJ,Tsai M, IgE and mast cells in allergic disease. Nature medicine. 2012 May 4;     [PubMed PMID: 22561833]

Level 3 (low-level) evidence


Wilcock LK,Francis JN,Durham SR, IgE-facilitated antigen presentation: role in allergy and the influence of allergen immunotherapy. Immunology and allergy clinics of North America. 2006 May     [PubMed PMID: 16701148]


Amarasekera M. Immunoglobulin E in health and disease. Asia Pacific allergy. 2011 Apr:1(1):12-5. doi: 10.5415/apallergy.2011.1.1.12. Epub 2011 Apr 19     [PubMed PMID: 22053291]


Justiz Vaillant AA,Zito PM, Immediate Hypersensitivity Reactions 2019 Jan;     [PubMed PMID: 30020687]


Thomsen SF, Atopic dermatitis: natural history, diagnosis, and treatment. ISRN allergy. 2014;     [PubMed PMID: 25006501]


Darsow U,Ring J, Immunoglobulin e-mediated allergy plays a role in atopic eczema as shown in the atopy patch test. The World Allergy Organization journal. 2008 Mar;     [PubMed PMID: 23283386]


Liu FT,Goodarzi H,Chen HY, IgE, mast cells, and eosinophils in atopic dermatitis. Clinical reviews in allergy     [PubMed PMID: 21249468]

Level 3 (low-level) evidence


McSorley HJ,Maizels RM, Helminth infections and host immune regulation. Clinical microbiology reviews. 2012 Oct;     [PubMed PMID: 23034321]

Level 3 (low-level) evidence


Anthony RM,Rutitzky LI,Urban JF Jr,Stadecker MJ,Gause WC, Protective immune mechanisms in helminth infection. Nature reviews. Immunology. 2007 Dec;     [PubMed PMID: 18007680]

Level 3 (low-level) evidence


Kelly BT,Grayson MH, Immunoglobulin E, what is it good for? Annals of allergy, asthma     [PubMed PMID: 26945494]