Role of IgE in autoimmunity

Abstract

There is accumulating evidence to suggest that IgE plays a significant role in autoimmunity. The presence of circulating self-reactive IgE in patients with autoimmune disorders has been long known but, at the same time, largely understudied. However, studies have shown that the increased IgE concentration is not associated with higher prevalence for atopy and allergy in patients with autoimmune diseases, such as systemic lupus erythematosus. IgE-mediated mechanisms are conventionally known to facilitate degranulation of mast cells and basophils and promote TH2 immunity, mechanisms that are not only central to mounting an appropriate defense against parasitic worms, noxious substances, toxins, venoms, and environmental irritants but that also trigger exuberant allergic reactions in patients with allergies. More recently, IgE autoantibodies have been recognized to participate in the self-inflicted damaging immune responses that characterize autoimmunity. Such autoimmune responses include direct damage on tissue-containing autoantigens, activation and migration of basophils to lymph nodes, and, as observed most recently, induction of type 1 interferon responses from plasmacytoid dendritic cells. The importance of IgE as a central pathogenic mechanism in autoimmunity has now been clinically validated by the approval of omalizumab, an anti-IgE mAb, for patients with chronic spontaneous urticaria and for the clinical benefit of patients with bullous pemphigoid. In this review we summarize recent reports describing the prevalence of self-reactive IgE and discuss novel findings that incriminate IgE as central in the pathogenesis of inflammatory autoimmune disorders.

Interferon α2 and interferon γ induce the degranulation independent production of VEGF‐A and IL‐1 receptor antagonist and other mediators from human mast cells

“…These include hypoxic tissue microenvironments, complement receptors, toll‐like receptors and other innate immune recognition receptors 2. IgE mediated activation of dendritic cells has been associated with enhanced IFN production in systemic lupus but limits IFN expression following TLR‐mediated activation 54, 55, 56. These findings suggest a potentially complex relationship between IgE, dendritic cells, mast cells, and IFNs in disease.…”

Justification for IgE as a therapeutic target in chronic spontaneous urticaria

“…In SLE, serum IgE correlates with disease activity, and consequently a pathogenic role for IgE has been proposed (1,30). IgE autoantibodies to nucleic acids (dsDNA, Sm, SS-A, SS-B) are present in SLE, and anti-double stranded DNA (dsDNA) IgE is associated with disease activity, hypocomplementemia and nephritis (30).…”

“…Self-reactive IgE autoantibodies are also present in bullous pemphigoid, CSU and atopic dermatitis. IgE autoantibodies contribute to the direct damage on autoantigen-containing tissues, activation and migration of basophils to the lymph nodes, and induction of type 1 interferon responses from plasmacytoid dendritic cells (1,31).…”

“…IgE-mediated autoimmunity is present in various autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, bullous pemphigoid, and CSU (1). It has been reported that chronic urticaria is associated with the increase of total and allergen-specific IgE (2-7), basopenia, and basophil phenotypic abnormalities (8)(9)(10)(11)(12).…”

Rapid fluorescence detection of immunoglobulin E using an aptamer switch based on a binding-induced pyrene excimer

“…[1][2][3][4][5][6] Sensitive and selective detection of human IgE is of great importance. Immunoassays are one of the commonly used methods for IgE detection, [7][8][9] which use antibodies as affinity ligands.…”