IgE autoreactivity in bullous pemphigoid: eosinophils and mast cells as major targets of pathogenic immune reactants

• Published in: British journal of dermatology (1951) Vol. 177; no. 6; pp. 1644 - 1653
• Main Authors: Freire, P.C., Muñoz, C.H., Stingl, G.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.12.2017; John Wiley and Sons Inc
• Subjects: Autoantibodies; Autoantigens - metabolism; Autoantigens - physiology; Autoimmune diseases; Autoimmunity - immunology; Basophils - immunology; Bullous pemphigoid; Cell Communication - immunology; Cell Degranulation - immunology; Cohort Studies; Collagen Type XVII; Degranulation; Dermis - metabolism; Enzyme-linked immunosorbent assay; Eosinophils - immunology; Humans; Immunofluorescence; Immunoglobulin E; Immunoglobulin E - immunology; Immunoglobulin E - metabolism; Immunoglobulin G; Leukocytes (basophilic); Leukocytes (eosinophilic); Mast cells; Mast Cells - immunology; Non-Fibrillar Collagens - metabolism; Non-Fibrillar Collagens - physiology; Original; Pemphigoid, Bullous - immunology; Pruritus; Skin; Steroid hormones; Structure-function relationships; Translational Research
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.15924

Summary Background Bullous pemphigoid (BP) is an autoimmune disease characterized by tense blisters that are usually preceded by urticarial eruptions. Affected patients exhibit IgG and/or IgE autoantibodies against BP180 and/or BP230. Their relative importance in disease pathogenesis has not been fully elucidated. Objectives The aim of this study was to provide a better characterization of the circulating and tissue‐resident IgE in patients with BP at the serological, structural and functional levels. Methods Sera (n = 19) and skin (n = 33) from patients with BP were analysed via enzyme‐linked immunosorbent assay (ELISA) and immunofluorescence, respectively. Results The results obtained show that many patients with BP exhibit elevated IgE levels in the serum and in the skin. In the skin, it is very rarely and only sparsely found along the basement membrane zone, but is prominently present on mast cells and eosinophils. At least a portion of these IgE antibodies are BP‐specific, as evidenced by serum ELISA and by the colocalization of BP180 and FcεRI‐bound IgE on mast cells and/or eosinophils. An important role of these immune reactants can be inferred from our additional finding that cross‐linking of IgE, derived from BP sera, on FcεRI‐expressing rat basophils with BP180 results in robust degranulation of these cells. Conclusions We propose the existence of a disease pathway alternative to IgG and complement that may well be responsible for some of the clinical features of this autoimmune disease. What's already known about this topic? Patients with bullous pemphigoid (BP) very often present with pruritus and hives. Circulating disease‐specific IgE is characteristic of patients with BP and correlates with urticarial lesions. What does this study add? This study demonstrates that IgE is found not only in the serum, but also in the perilesional skin of patients with BP, colocalizing with mast cells, eosinophils and BP180 fragments. Antigenic peptides of BP180 are capable of cross‐linking FcεRI‐bound IgE, ultimately resulting in degranulation. What is the translational message? IgE‐mediated events likely influence the onset and development of BP symptoms. Uncovering an IgE‐dependent disease pathway might impact therapeutic options and reduce the burden of steroids in this aged population. Linked Comment: Ujiie. Br J Dermatol 2017; 177:1481–1482. Plain language summary available online Respond to this article