Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
Role of mast cells in allergy had remained undetermined until the discovery of IgE in 1966. Then, IgE purified from many Liters of plasma, which had been donated from a patient with fatal myeloma, was distributed to researchers all over the world (http://buff.ly/12sD3cO).
IgE is involved in immediate hypersensitivity (allergy). It binds to allergens and triggers histamine release from mast cells. It has the lowest serum concentration (mcg rather than mg) and the shortest half-life (2 days) among Ig (GAMED).
Controls of Ig type switch
IgA switching: APRIL, BAFF, TGF-beta
IgE switching: IL-4
IgG switching: IFN-gamma
There are 5 immunoglobulin classes remembered by the mnemonic GAMED: Ig G, A, M, E, D. B-cells are the only cell types that synthesize antibody molecules.
Five immunoglobulin classes (mind map).
In order of their serum concentrations:
IgG 1000 mg/dL
IgA 200 mg/dL
IgM 150 mg/dL
IgD 4 mg/dL
IgE 0.005 mg/dL (extremely low serum concentration compared to other Ig in (GAMED)
Measurement of total IgE is expressed in 1 IU/mL = 2.44 ng/mL.
There are 5 immunoglobulin classes remembered by the mnemonic GAMED: Ig G, A, M, E, D. B-cells are the only cell types that synthesize antibody molecules.
Five immunoglobulin classes (mind map).
In order of their serum concentrations:
IgG 1000 mg/dL
IgA 200 mg/dL
IgM 150 mg/dL
IgD 4 mg/dL
IgE 0.005 mg/dL (extremely low serum concentration compared to other Ig in (GAMED)
Measurement of total IgE is expressed in 1 IU/mL = 2.44 ng/mL.
The level of IgE increases during childhood until about 10 years of age. At age 10, the total IgE reaches a value that is typically maintained throughout adult life.
Ig order of their serum half-life in days:
IgG 21
IgM 10
IgA 6
IgD 3
IgE 2 (shortest half-life among other Ig in GAMED)
Ig order of their serum half-life in days:
IgG 21
IgM 10
IgA 6
IgD 3
IgE 2 (shortest half-life among other Ig in GAMED)
Role of IgE and mast cells in allergy. Image source: Wikipedia.
Omalizumab binds to Cε3 region of IgE.
IL-4 and IL-13 are cytokines produced by Th2 cells. They up-regulate IgE production and thus increase allergic inflammation. IL-4 is much more potent than IL-13.
I
IL-4
IL-13
Increase
IgE production
Inflammation promoters
Receptors for IgE
High-Affinity IgE Receptor (FcεRI)
The high affinity receptor for IgE (FcεRI) is expressed on mast cells (fixed in tissues) and basophils (circulating in blood). The level of FcεRI expression is regulated by levels of IgE. FcεRI molecule consists of 4 chains: alpha, beta and 2 gamma.
FcεRI is found in 2 forms:
- tetrameric form is composed of one α chain, one β chain, and two γ chains. It is found on mast cells, basophils, eosinophils.
- trimeric form is composed of one α chain and two γ chains. It is found on monocytes and dendritic cells (the β chain is absent).
Some patients with chronic urticaria have IgG directed against the α chain of FcεRI. IgE binds to FcεRI via the α chain.
CD23 is the low affinity IgE receptor (FceRII). CD21 (CR2) binds EBV, HHV8, C3d, and CD23 (low affinity IgE receptor (FceRII).
The role of FcεRII is not clear. Variations in the low-affinity IgE receptor gene (FCER2 or II) are associated with an increase in severe exacerbations in children with asthma. There are several reasons that a patient may not respond to inhaled corticosteroid therapy in asthma and genetics, including FCER2 variants, may be an important one.
Variations in some of the SNPs were associated with increased IgE levels and increased risk of severe exacerbations of asthma during inhaled corticosteroid treatment. Therefore, FCER2 variations may lead to asthma exacerbations despite inhaled steroids. Personalized medicine via pharmacogenetics can lead to genetic studies guiding therapeutic decisions in the future.
Anti-IgE (omalizumab, Xolair) is approved for treatment of severe persistent asthma. There are occasional case reports of anti-IgE (omalizumab) use as a new therapeutic approach for chronic rhinosinusitis. Omalizumab binds to Cε3 region of IgE.
There is a correlation between IgE titres and the severity of clinical reaction to egg after the diagnosis has been established. A cut-off level of 8.20 kU/l had a 90% probability of clinical reactivity. IgE titres may help determine which patients are at risk of a reaction to eggs.
Higher levels of IgE are associated with more severe asthma (the cut-off level is 100 IU/mL). IgE level is inversely correlated with baseline lung function and asthma severity.
ImmunoCAP Immunoassay
The ImmunoCAP method was developed by Phadia. It utilizes a “sandwich” ELISA technique:
1. The ImmunoCAP sponge has allergen bound to it and serves as the first piece of bread ("bottom half").
2. Patient serum is added and specifc IgE to that allergen binds to the allergen on the sponge - this is the "meat" of the ELISA sandwich.
3. All of the unbound protein is washed away abd anti-IgE is added - this binds to the sIgE that was captured by the sponge in step two. The anti-IgE conjugate is the "second piece of bread" ("top half").
Allergen-specific IgE levels are not comparable between different laboratory methods - for example, ImmunoCAP vs. DPC Immulite 2000. Predictive values of specific IgE levels published in the literature for management of food allergies are based on studies using the ImmunoCAP assay. These predictive values cannot be applied to specific IgE levels from other assay systems.
Conditions with elevated IgE
Atopic dermatitis, Asthma, ABPA, and allergic fungal sinusitis
Infections (parasites, HIV, TB, EBV, and CMV)
Malignancy (IgE myeloma and lymphoma)
Churg-Strauss syndrome
Kimura’s disease, painless, unilateral cervical lymphadenopathy or subcutaneous masses in the head or neck region
Immunodeficiency diseases with elevated IgE
Hyper IgE syndrome (HIES)
Wiskott-Aldrich syndrome (WAS)
Omenn syndrome
DiGeorge syndrome (DGS)
Netherton syndrome, form of ichthyosis associated with SPINK5
Nezelof syndrome, congenital hypoplasia of the thymus with retention of normal parathyroid function (in contrast to complete DiGeorge syndrome in which there is absence of the parathyroids)
Published: 06/28/2010
Updated: 09/16/2012
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