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

Background Bullous pemphigoid (BP) is an autoimmune disease characterised by tense blisters that are usually preceded by urticarial eruptions. Affected patients exhibit IgG and/or IgE auto-antibodies against BP180 and/or BP230. Their relative importance in disease pathogenesis has not been fully elucidated. Objectives The aim of this study was to better characterise circulating and tissue-resident IgE in BP patients at the serological, structural and functional level. Methods Sera (n=19) and skin (n=33) from BP patients were analysed via ELISA and immunofluorescence, respectively. Results Results obtained show that BP patients exhibit elevated IgE levels in the serum and in the skin. Within the latter, it is very rarely and only sparsely found along the basement membrane zone (BMZ), 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 co-localization of BP180 and FceRI-bound IgE on mast cells and/or eosinophils. An important role of these immune reactants can be implied by our additional finding that cross-linking of IgE, derived from BP sera, on FceRI-expressing rat basophils with BP180 results in robust degranulation of these cells. Conclusion 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. This article is protected by copyright. All rights reserved.