title: Large-Scale Electron Microscopy Maps of Patient Skin and Mucosa Provide Insight into Pathogenesis of Blistering Diseases.
abstract: Large-scale electron microscopy ("nanotomy") allows straight forward ultrastructural examination of tissue, cells, organelles, and macromolecules in a single data set. Such data set equals thousands of conventional electron microscopy images and is freely accessible (www.nanotomy.org). The software allows zooming in and out of the image from total overview to nanometer scale resolution in a 'Google Earth' approach. We studied the life-threatening human autoimmune blistering disease pemphigus, using nanotomy. The pathomechanism of cell-cell separation (acantholysis) that underlies the blistering is poorly understood. Ultrastructural examination of pemphigus tissue revealed previously unreported findings: (i) the presence of double-membrane structures between cells in all pemphigus types; (ii) the absence of desmosomes around spontaneous blisters in pemphigus foliaceus (PF); (iii) lower level blistering in PF when force induced; and (iv) intercellular widening at non-acantholytic cell layers. Thus, nanotomy delivers open-source electron microscopic maps of patient tissue, which can be analyzed for additional anomalies from any computer by experts from different fields.
authors: Department of Cell Biology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands; Department of Dermatology, Center for Blistering Diseases, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
authors: Ena
authors: E
authors: Sokol
authors: Department of Dermatology, Center for Blistering Diseases, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
authors: Duco
authors: D
authors: Kramer
authors: Department of Dermatology, Center for Blistering Diseases, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
authors: Gilles F H
authors: GFH
authors: Diercks
authors: Department of Cell Biology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
authors: Jeroen
authors: J
authors: Kuipers
authors: Department of Dermatology, Center for Blistering Diseases, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
authors: Marcel F
authors: MF
authors: Jonkman
authors: Department of Dermatology, Center for Blistering Diseases, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
authors: Hendri H
authors: HH
authors: Pas
authors: Department of Cell Biology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: b.n.g.giepmans@umcg.nl.
authors: Ben N G
authors: BNG
authors: Giepmans
mesh_terms: D000051:Acantholysis / Q000473:pathology; D001707:Biopsy, Needle; D001768:Blister / Q000473:pathology; D016022:Case-Control Studies; D003896:Desmosomes / Q000473:pathology / Q000648:ultrastructure*; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron / Q000379:methods; D009061:Mouth Mucosa / Q000473:pathology / Q000648:ultrastructure; D049329:Nanostructures; D010392:Pemphigus / Q000473:pathology* / Q000503:physiopathology; D012016:Reference Values; D012680:Sensitivity and Specificity; D012867:Skin / Q000473:pathology / Q000648:ultrastructure*; D012872:Skin Diseases, Vesiculobullous / Q000473:pathology / Q000503:physiopathology