@article{GoebelerBataCsoergőSimoneetal.2022,
  author    = {Goebeler, M. and Bata-Cs{\"o}rgő, Z. and Simone, C. de and Didona, B. and Remenyik, E. and Reznichenko, N. and Stoevesandt, J. and Ward, E. S. and Parys, W. and Haard, H. de and Dupuy, P. and Verheesen, P. and Schmidt, E. and Joly, P.},
  title     = {Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase II multicentre, open-label feasibility trial},
  series = {British Journal of Dermatology},
  volume    = {186},
  journal   = {British Journal of Dermatology},
  number    = {3},
  doi       = {10.1111/bjd.20782},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258328},
  pages     = {429-439},
  year      = {2022},
  abstract  = {Background Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. There is an unmet need for fast-acting drugs that enable patients to achieve early sustained remission with reduced corticosteroid reliance. Objectives To investigate efgartigimod, an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor, thereby reducing serum IgG levels, for treating pemphigus. Methods Thirty-four patients with mild-to-moderate pemphigus vulgaris or foliaceus were enrolled in an open-label phase II adaptive trial. In sequential cohorts, efgartigimod was dosed at 10 or 25 mg kg\(^{-1}\) intravenously with various dosing frequencies, as monotherapy or as add-on therapy to low-dose oral prednisone. Safety endpoints comprised the primary outcome. The study is registered at ClinicalTrials.gov (identifier NCT03334058). Results Adverse events were mostly mild and were reported by 16 of 19 (84\%) patients receiving efgartigimod 10 mg kg\(^{-1}\) and 13 of 15 (87\%) patients receiving 25 mg kg-1, with similar adverse event profiles between dose groups. A major decrease in serum total IgG and anti-desmoglein autoantibodies was observed and correlated with improved Pemphigus Disease Area Index scores. Efgartigimod, as monotherapy or combined with prednisone, demonstrated early disease control in 28 of 31 (90\%) patients after a median of 17 days. Optimized, prolonged treatment with efgartigimod in combination with a median dose of prednisone 0·26 mg \(^{-1}\) per day (range 0·06-0·48) led to complete clinical remission in 14 of 22 (64\%) patients within 2-41 weeks. Conclusions Efgartigimod was well tolerated and exhibited an early effect on disease activity and outcome parameters, providing support for further evaluation as a therapy for pemphigus.},
  language  = {en}
}
@article{SchmidtSticherlingSardyetal.2020,
  author    = {Schmidt, Enno and Sticherling, Michael and S{\´a}rdy, Mikl{\´o}s and Eming, R{\"u}diger and Goebeler, Matthias and Hertl, Michael and Hofmann, Silke C. and Hunzelmann, Nicolas and Kern, Johannes S. and Kramer, Harald and Nast, Alexander and Orzechowski, Hans-Dieter and Pfeiffer, Christiane and Schuster, Volker and Sitaru, Cassian and Zidane, Miriam and Zillikens, Detlef and Worm, Margitta},
  title     = {S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid: 2019 update},
  series = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft},
  volume    = {18},
  journal   = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft},
  number    = {5},
  doi       = {10.1111/ddg.14097},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217806},
  pages     = {516 -- 526},
  year      = {2020},
  language  = {en}
}
@article{HartliebKempfPartillaetal.2013,
  author    = {Hartlieb, Eva and Kempf, Bettina and Partilla, Miriam and Vigh, Bal{\´a}zs and Spindler, Volker and Waschke, Jens},
  title     = {Desmoglein 2 Is Less Important than Desmoglein 3 for Keratinocyte Cohesion},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {1},
  doi       = {10.1371/journal.pone.0053739},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131192},
  pages     = {e53739},
  year      = {2013},
  abstract  = {Desmosomes provide intercellular adhesive strength required for integrity of epithelial and some non-epithelial tissues. Within the epidermis, the cadherin-type adhesion molecules desmoglein (Dsg) 1-4 and desmocollin (Dsc) 1-3 build the adhesive core of desmosomes. In keratinocytes, several isoforms of these proteins are co-expressed. However, the contribution of specific isoforms to overall cell cohesion is unclear. Therefore, in this study we investigated the roles of Dsg2 and Dsg3, the latter of which is known to be essential for keratinocyte adhesion based on its autoantibody-induced loss of function in the autoimmune blistering skin disease pemphigus vulgaris (PV). The pathogenic PV antibody AK23, targeting the Dsg3 adhesive domain, led to profound loss of cell cohesion in human keratinocytes as revealed by the dispase-based dissociation assays. In contrast, an antibody against Dsg2 had no effect on cell cohesion although the Dsg2 antibody was demonstrated to interfere with Dsg2 transinteraction by single molecule atomic force microscopy and was effective to reduce cell cohesion in intestinal epithelial Caco-2 cells which express Dsg2 as the only Dsg isoform. To substantiate these findings, siRNA-mediated silencing of Dsg2 or Dsg3 was performed in keratinocytes. In contrast to Dsg3-depleted cells, Dsg2 knockdown reduced cell cohesion only under conditions of increased shear. These experiments indicate that specific desmosomal cadherins contribute differently to keratinocyte cohesion and that Dsg2 compared to Dsg3 is less important in this context.},
  language  = {en}
}