title: Pemphigus Autoantibodies Induce Blistering in Human Conjunctiva.
abstract: OBJECTIVE
  The autoimmune blistering skin disease pemphigus vulgaris (PV) is caused by autoantibodies against desmosomal adhesion molecules. Patients may suffer conjunctival involvement, yet the underlying mechanisms are largely unclear. We characterized human and murine conjunctiva with respect to the PV autoantigens, and evaluated the effects and mechanisms of PV autoantibodies applied to human conjunctiva ex vivo.
  
  
  METHODS
  We obtained human conjunctiva specimens from surgical explants and established a short-term culture model to study the alterations induced by antibody fractions of PV patients (PV-IgG). Furthermore, we applied a mouse model depleted of the desmosomal cadherin desmoglein 3 (Dsg3), the primary autoantigen in PV. Murine and human conjunctiva also was used to analyze the expression pattern of desmosomal proteins by immunostaining and Western blotting.
  
  
  RESULTS
  Human and murine conjunctiva samples expressed the majority of desmosomal molecules with an expression pattern similar to the epidermis. Interestingly, Dsg3 knock out animals frequently suffer eye lesions, histologically evident as microblisters in the eyelid epidermis and conjunctiva. Incubation of human specimens with PV-IgG for 12 hours caused blistering in the suprabasal layers of the conjunctiva as well as reduction of Dsg1 and Dsg3 protein levels. Furthermore, PV-IgG prompted activation of p38MAPK in the conjunctiva, which is a central pathomechanism leading to blistering in the epidermis.
  
  
  CONCLUSIONS
  PV-IgG leads to blister formation and p38MAPK activation in the conjunctiva and, thus, resembles the effects found in the epidermis. Our data indicate that the ocular involvement observed in PV patients is mainly based on conjunctival blistering.
authors.affiliation: Institute of Anatomy and Cell Biology Department I, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Vielmuth
authors.affiliation: Institute of Anatomy and Cell Biology Department I, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Rötzer
authors.affiliation: Institute of Anatomy and Cell Biology Department I, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Hartlieb
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hirneiß
authors.affiliation: Institute of Anatomy and Cell Biology Department I, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Waschke
authors.affiliation: Institute of Anatomy and Cell Biology Department I, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Spindler
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001768:Blister / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D003228:Conjunctiva / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051184:Desmoglein 3 / Q000378:metabolism; D003896:Desmosomes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010392:Pemphigus / Q000150:complications / Q000175:diagnosis / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015820:Cadherins; D051184:Desmoglein 3