Pemphigus

Pemphigus is a severe disease characterized by blistering of skin and/or mucosa which is 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). 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.

Dissertation: http://hdl.handle.net/11370/7c13126b-024c-43a4-ab34-ffd0b0081878