Immunoglobulin E-Mediated Autoimmunity

Abstract

The study of autoimmunity mediated by immunoglobulin E (IgE) autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP), and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.

Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study

“…The first suggestion that CSU may have an autoimmune basis came from Rorsman in 1962, who suggested an antigen‐antibody reaction as a potential cause of the observed peripheral blood basopenia. It has subsequently been proposed that this autoimmunity may have two possible forms, Type I and Type IIb …”

“…It has subsequently been proposed that this autoimmunity may have two possible forms, Type I and Type IIb. [3][4][5][6] A possible role of IgE-mediated Type I autoimmunity, also referred to as autoallergy, was postulated following observations of IgE autoantibodies to thyroperoxidase. 7 More recently, CSU patients have also been shown to have IgE against double-stranded DNA, 8 interleukin-24, 9 tissue factor, and thyroglobulin.…”

Immunological effects and potential mechanisms of action of autologous serum therapy in chronic spontaneous urticaria

“…CSU, in many patients, is held to be an autoimmune disorder and is linked to the presence of mast cell-degranulating autoantibodies, either IgE autoantibodies directed to autoallergens (type I autoimmunity) or IgG autoantibodies to the high-affinity IgE receptor or IgE itself (type IIb autoimmunity). 4 Our hypothesis was that autohemotherapy, in patients who benefit from this treatment, reduces the levels and/or effects of these mast cell-degranulating IgE and IgG autoantibodies. Our results strongly suggest that autohemotherapy reduces the levels of IgE autoantibodies, but not the levels or effects of IgG autoantibodies.…”

“…The pathomechanisms of CSU have been studied for decades, but remain not fully understood. Nowadays, two types of autoimmune mechanisms are held to be relevant in many cases of CSU: type I autoimmunity (also called autoallergy) with immunoglobulin E (IgE) autoantibodies to autoantigens and type IIb autoimmunity with immunoglobulin G (IgG) autoantibodies to IgE or its high‐affinity receptor, FcεRI . The autologous serum skin test (ASST) is used as a non‐specific screening test to evaluate the presence of histamine‐releasing factors in serum.…”

Type VII collagen IgE autoantibodies in epidermolysis bullosa acquisita: more common than suspected

“…Regarding IgE autoantibodies, several groups confirmed the presence of circulating and tissue‐bound IgE autoantibodies in BP, mainly targeting BP180‐NC16A. The prevalence of these IgE autoantibodies in patients with BP ranges from 22% to 100% . Injection of total IgE isolated from patients with BP into human skin grafted onto immunodeficient mice induced dermal infiltration and subepidermal blistering in the grafts, pointing towards a potential pathogenic role of IgE autoantibodies in BP .…”