Eikmans, H. (Hugo) (2012) DE ROL VAN mTOR IN DE PATHOGENESE VAN PEMPHIGUS VULGARIS. thesis, Medicine.
Full text available on request.Abstract
Pemphigus vulgaris (PV) is a severe auto-immune blistering disease. Auto-antibodies are directed against the desmosomal components desmoglein 1 and/or desmoglein 3. These auto-antibodies induce loss of cell-cell adhesion (acantholysis). A recent study in mice linked the activation of the kinase mammalian target of rapamycin (mTOR) to acantholysis. Our aim was to determine the role of mTOR in PV in humans. Using immunofluorescence staining we compared the amount of activated mTOR (p-mTOR) in sections of acantholytic skin and non- acantholytic skin of PV patients and skin of control patients. We also used a pemphigus in vitro model. The p-mTOR levels varied considerably in our control group. Only 1 of 4 PV patients showed more p-mTOR in acantholytic skin compared to non-acantholytic PV skin. 3 of 8 PV patients showed increased p-mTOR levels in non-lesional skin compared to control skin. In our in vitro skin model we incubated healthy skin biopsies with PV or control IgG for 24 hours to induce acantholysis. After 24 hours p-mTOR levels were not significantly higher in acantholytic skin. Furthermore we looked at mTOR activation at different timepoints within 24 hours. This showed a peak after 4 and 16 hours. We also investigated whether sirolimus, an inhibitor of mTOR activation, could prevent acantholysis in our PV in vitro model. A sirolimus dose of 2000 ng/ml inhibited acantholysis. In conclusion there is no clear association between activation of mTOR and acantholysis in vivo and in vitro after 24 hours. It could be that there is an early activation peak. Sirolimus was able to inhibit acantholysis in our in vitro model. So the role of mTOR in PV cannot definitively be excluded.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Dagelijks begeleider: and Poot, Angelique and Facultair begeleider: and Pas, Hendri and Afdeling: centrum voor blaarziekten, afdeling dermatologie |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:00 |
| Last Modified: | 25 Jun 2020 11:00 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2033 |
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