@phdthesis{HerreroGonzalez2007,
  author    = {Herrero-Gonz{\´a}lez, Josep E.},
  title     = {Pathogenic relevance of autoantibodies to type XVII collagen from pemphigoid gestationis patients},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-22329},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Pemphigoid gestationis (PG) and bullous pemphigoid (BP) are subepidermal autoimmune blistering diseases characterized by self-reactive T and B cells specific for the transmembrane hemidesmosomal protein type XVII collagen/BP180. Major T and B cell epitopes are located within the immunodominant 16th non-collagenous domain A (NC16A) of type XVII collagen. It has been suggested that pathogenically relevant autoantibodies also bind to this immunodominant region. The aim of this study was to map the epitopes targeted by blister-inducing human autoantibodies. For this purpose, we used an in vitro model of autoantibody-induced leucocyte-dependent dermal-epidermal separation. In contrast to the majority of patients with BP (7 of 10), preadsorption against a recombinant form of the NC16A region abolished the blister-inducing potential of autoantibodies from all PG patients tested (n=5). Using overlapping synthetic peptides, we demonstrate that PG autoantibodies bind to 2 defined epitopes within the NC16A region (aa 500-514 and aa 511-523). Preadsorption using an affinity matrix containing these two epitopes completely abolished dermal-epidermal separation induced by PG autoantibodies (in 8 of 9 patients). These findings provide new insights into the pathogenesis of pemphigoid diseases and should prove helpful for the development of an antigen-specific immunoadsorption therapy in PG.},
  language  = {en}
}