Publication

Pemphigus pathogenesis: Insights from light and electron microscopy studies

Sokol, E., 2016, [Groningen]: University of Groningen. 148 p.

Research output: ThesisThesis fully internal (DIV)

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Documents

  • Ena Sokol
Pemphigus is a life-threatening autoimmune blistering disease caused by antibodies against proteins of desmosomes. Desmosomes are adhesion junctions that interconnect intermediate filament networks of neighboring cells. By targeting transmembrane proteins of desmosomes, desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3), pemphigus autoantibodies induce their clustering and loss of cell-cell adhesion (acantholysis) in the epidermis of the skin and epithelium of the mucosal membranes, which results in blistering. How pemphigus autoantibodies induce blisters is the main research question of this thesis. Skin and mucosa taken from pemphigus patients were analyzed using large scale electron microscopy, named ‘’nanotomy’’ and novel findings are described. The datasets are open source available at www.nanotomy.org. Pemphigus skin was further investigated using an overlay of light and electron microscopy showing that desmoglein clusters are interdigitations between cells in which the amount of Dsg1 in desmosomes is reduced. Lastly antibodies from pemphigus patients were applied to cultured human skin cells, revealing redistribution of the targeted desmogleins in specific patterns. This thesis suggests that loss of cell-cell adhesion in pemphigus occurs due to the depletion of the targeted desmogleins which then cannot be incorporated into the desmosomes. If other desmoglein isoform are not expressed, desmosomes will ‘melt’ away resulting in loss of cell-cell adhesion.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
  • Jonkman, Marcellinus, Supervisor
  • Pas, Hendri, Co-supervisor
  • Giepmans, Ben, Co-supervisor
  • Peters, P.J., Assessment committee, External person
  • Ludwig, R., Assessment committee, External person
  • Heeringa, Peter, Assessment committee
Award date6-Jan-2016
Place of Publication[Groningen]
Publisher
Print ISBNs978-94-6259-982-6
Publication statusPublished - 2016

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