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

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Abstract

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.

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