IgE-mediated mechanisms

When exposure is repeated, the allergen binds between two adjacent IgE molecules. This causes release of inflammatory mediators (histamine, leukotrienes, chemotactic factors). These act locally and cause smooth muscle contraction, increased vascular permeability, mucous gland secretion, and infiltration of inflammatory cells (neutrophils and eosinophils). However, histamine can also be released by non-IgE-mediated mechanisms (e.g., due to exposure to certain fungi). 463... 

In addition to the proteins discussed above, a large number of reactive chemicals used in industry can cause asthma and rhinitis. Hypersensitivity pneumonias have also been described. Isocyanates and acid anhydrides are industrial chemicals that cause occupational asthma. Acid anhydrides, such as phthalic anhydride, seem to cause mainly type I reactions, whereas the IgE-mediated mechanism explains only a part of the sensitizations to isocyanates. Several mechanisms have been suggested, but despite intensive research no models have been generally accepted. The situation is even more obscure for other sensitizing chemicals therefore, the term specific chemical hypersensitivity is often used for chemical allergies. This term should not be confused with multiple chemical sensitivity (MCS) syndrome, which is a controversial term referring to hypersusceptibility to very low levels of environmental chemicals. ... 

The mechanisms of the allergy-like reactions to RCM are still a matter of speculation (table 2). Anaphylaxis to RCM has been discussed to be due to a direct membrane effect possibly related to the osmolality of the RCM solution or the chemical structure of the RCM molecule (pseudo-allergy) [2], an activation of the complement system [27], a direct bradykinin formation [28], or an IgE-mediated mechanism [3]. 

Two anaphylactic reactions have been reported, one after intra-articular injection, the other after submucosal bladder injection of orgotein. An IgE-mediated mechanism was demonstrated in the first case (SEDA-12, 94) (SEDA-14, 96). 

Metabisulfite-induced anaphylaxis through an IgE-mediated mechanism has been described in a patient who developed urticaria, angioedema, and nasal congestion following provocative challenge with sodium metabisulfite (6). 

Allergy to vitamin B12 injection is infrequent, but can be serious. Positive results of basophil histamine release assay and skin testing suggest an IgE-mediated mechanism (5). Severe hypersensitivity to cyanoco-balamin or hydroxocobalamin has been reported in patients who took the other cobalamin without further allergic reactions (6). 

Allergic Asthma. It is the basic term for asthma mediated by immunological mechanisms. When there is evidence of IgE-mediated mechanisms the term IgE-mediated asthma is recommended. IgE antibodies can initiate both an immediate and a late asthmatic reaction. However, as in other allergic disorders, T-cell-associated reactions seem to be of importance in the late and delayed reactions. Depending on the duration of symptoms, asthma can be referred to as either intermittent or persistent (as recommended in the document Allergic Rhinitis and Its Impact on Asthma [3]). 

Any drug that can cause IgE-mediated allergy and anaphylactic reactions can also be responsible for bronchospasm (Charpin et al. 1972). However, this is seldom the only manifestation of allergy, unless the drug is delivered to the lungs by aerosol of by inhalation as a powder. Enzymes and macromolecular components such as pituitary snuff are well known to produce sensitization of that type. Sensitization to simple chemicals such as penicillin (Davies et al. 1974), spiramycin (Davies and Pepys 1975), or phenylmercuric propionate (Mathews and Pan 1968) can lead to asthmatic reactions through IgE-mediated mechanisms. The same has been described for the inhalation of other low-molecular-weight chemicals such as diisothiocyanate and platinum salts encountered in industrial applications (Pepys and Davies 1978). 

Immunologic-type agents are confirmed by specific positive radioallergosorbent tests (RASTs) and by negative tests on control subjects, rarely by passive transfer tests (Prausnitz-Kiistner tests) in animals. In vitro tests can also be used to assess the relationship with a possible IgE-mediated mechanism, namely, determination of histamine release from peripheral basophils or platelet cytotoxicity test, which explores the presence on platelets of specific IgE antibodies bound to the low-affinity receptor for IgE. 

Steiner M, Harrer A, Lang R, et al. Basophil activation test for investigation of IgE-mediated mechanisms in drug hypersensitivity. J Vis Exp. 201 l 55 e3263. doi 10.3791/3263. 

In this chapter we provide an overview of the current cellular and molecular mechanisms involved in airway inflammation, in particular the involvement of IgE-mediated mechanisms, and the application of novel therapeutic agents to suppress ongoing airway inflammatory responses in asthma. 

Figure 2 Schematic representation of possible IgE-mediated mechanisms for the late phase response involving mast cell-dependent and mast cell-independent pathways. Inhalation of aeroallergen may cause IgE-dependent activation of mast cells leading directly or indirectly to the late phase response (pathway A). Alternatively, there is evidence that inhalation of aeroallergen may cause activation of CD4-I- T cells and a subsequent late phase response through a process of IgE-facilitated antigen presentation or IgE-dependent antigen focusing of allergen to CD4-I- T cells by IgE receptor-bearing dendritic cells (pathway B).

Avoidance measures and oral double-blinded, placebo-controlled food challenges may be necessary to confirm the role of an allergen. Other substances may induce urticaria by non-IgE-mediated mechanisms, like additives, aspirin or... 

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