Nanotomie van huid en mucosa van pemfiguspatiënten

Pemphigus is an auto-immune blistering skin and/or mucosal disease caused by antibodies against proteins of desmosomes. Desmosomes are cell-cell adhesion structures that interconnect intermediate filament networks of neighboring cells. The transmembrane desmosomal proteins that are the targets of pemphigus autoantibodies, desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3), are specific for the stratified epithelia of the skin and mucosal membranes and are not present in the simple epithelia. Therefore, loss of cell-cell adhesion (acantholysis) induced by pemphigus autoantibodies and clinically presented as blistering occurs only in these tissues. Two main forms of pemphigus are known: pemphigus vulgaris (PV) and pemphigus foliaceus (PF) with a different clinical picture and a different autoantibody profile. How pemphigus autoantibodies induce loss of cell-cell adhesion is our main question. Large scale electron microscopy ("nanotomy") was applied to study pemphigus patients skin and mucosa. This non-biased technique allows easy exploration of large tissue areas which is not possible by conventional EM. We examined both skin and mucosa of PF and PV patients, focusing on ultrastructural details: localization of blister, presence of half desmosomes and localization of keratin filament network in the cells surrounding the blister and desmosomes and intercellular space in nonlesional layers. In spontaneous lesional PF patient skin no desmosomes were present round the blister, while in Nikolsky positive PF patient skin half desmosomes were observed round the blister. In all lesional pemphigus samples and to a lesser extend in non-lesional samples newly described structures named interdigitations composed out of two neighboring cell membranes were present. These structures were abundant in lesional pemphigus skin, which provides a clue to blister pathogenesis.Open source electron-microscopic maps of pemphigus tissue are freely accessible at www.nanotomy.org.