Pemphigus: Insights in diagnosis and pathogenesis

Angelique Muriel Poot

    Research output: ThesisThesis fully internal (DIV)

    989 Downloads (Pure)

    Abstract

    Pemphigus is a severe disease characterized by blistering of skin and/or mucosa.
    These blisters are caused by autoantibodies directed against specific proteins in the skin. These proteins, called desmogleins, mediate cell-cell adhesion, and are part of a protein complex called the desmosome. Several pemphigus subtypes exist, including the rare but severe subtype paraneoplastic pemphigus (PNP), and the diagnosis of this subtype is challenging because its manifestations can mimic other diseases. Furthermore, there is much debate regarding the cellular mechanisms that lead to blister formation. In this thesis we aimed to improve the diagnosis of PNP, and to gain more insight into blister formation.
    We compared several laboratory techniques in their ability to detect autoantibodies in the serum of PNP patients, and found that combination of two relatively simple and cheap techniques, namely immunoblotting and indirect immunofluorescence microscopy on rat bladder, is a good alternative to the more elaborate technique of immunoprecipitation, as diagnostic tool. We furthermore used several microscopic techniques to examine desmogleins and desmosomes in the skin and mucosa of patients with pemphigus foliaceus, who develop blistering of only the skin. We found that specific desmogleins are rearranged into clusters outside of desmosomes. This leads to the shrinkage of desmosomes, even in intact oral mucosa. In addition, some patients experience worsened blistering after UV-exposure, and we found that in the skin of these patients, desmogleins are cleaved. In conclusion, these studies improve the diagnosis of PNP and advance our insights into the molecular aspects of blistering in pemphigus.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Jonkman, Marcellinus, Supervisor
    • Pas, Hendri, Co-supervisor
    Award date6-Jan-2016
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-90-367-8493-1
    Electronic ISBNs978-90-367-8492-4
    Publication statusPublished - 2016

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