Human IgE-independent systemic anaphylaxis

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:137

Article

Finkelman, Fred D.^1,2,3,4  Khodoun, Marat V.^1,3  Strait, Richard^2,5 

[1] Univ Cincinnati, Coll Med, Dept Internal Med, Div Allergy Immunol & Rheumatol, Cincinnati, OH 45208 USA

[2] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45208 USA

[3] Cincinnati Vet Affairs Med Ctr, Dept Med, Cincinnati, OH USA

[4] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA

[5] Cincinnati Childrens Hosp Med Ctr, Div Emergency Med, Cincinnati, OH 45229 USA

关键词: Anaphylatoxin;    complement;    Fc epsilon R;    Fc gamma R;    IgE;    IgG;    mast cell;    basophil;    mouse;   

DOI  :  10.1016/j.jaci.2016.02.015

来源: Elsevier

【 摘 要 】

Anaphylaxis is a rapidly developing, life-threatening, generalized or systemic allergic reaction that is classically elicited by antigen crosslinking of antigen-specific IgE bound to the high-affinity IgE receptor Fc epsilon RI on mast cells and basophils. This initiates signals that induce cellular degranulation with release and secretion of vasoactive mediators, enzymes, and cytokines. However, IgE-independent mechanisms of anaphylaxis have been clearly demonstrated in experimental animals. These include IgG-dependent anaphylaxis, which involves the triggering of mediator release by IgG/antigen complex crosslinking of Fc gamma Rs on macrophages, basophils, and neutrophils; anaphylaxis mediated by binding of the complement-derived peptides C3a and C5a to their receptors on mast cells, basophils, and other myeloid cells; and direct activation of mast cells by drugs that interact with receptors on these cells. Here we review the mechanisms involved in these IgE-independent forms of anaphylaxis and the clinical evidence for their human relevance. We conclude that this evidence supports the existence of all 3 IgE-independent mechanisms as important causes of human disease, although practical and ethical considerations preclude their demonstration to the degree of certainty possible with animal models. Furthermore, we cite evidence that different clinical situations can suggest different mechanisms as having a primal role in anaphylaxis and that IgE-dependent and distinct IgE-independent mechanisms can act together to increase anaphylaxis severity. As specific agents become available that can interfere with mechanisms involved in the different types of anaphylaxis, recognition of specific types of anaphylaxis is likely to become important for optimal prophylaxis and therapy.

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