title: Dermatitis herpetiformis sera or goat anti-transglutaminase-3 transferred to human skin-grafted mice mimics dermatitis herpetiformis immunopathology.
abstract: Dermatitis herpetiformis (DH) is characterized by deposition of IgA in the papillary dermis. However, indirect immunofluorescence is routinely negative, raising the question of the mechanism of formation of these immune deposits. Sárdy et al. (2002. J. Exp. Med. 195: 747-757) reported that transglutaminase-3 (TG3) colocalizes with the IgA. We sought to create such deposits using passive transfer of Ab to SCID mice bearing human skin grafts. IgG fraction of goat anti-TG3 or control IgG were administered i.p. to 20 mice. Separately, sera from seven DH patients and seven controls were injected intradermally. Biopsies were removed and processed for routine histology as well as direct immunofluorescence. All mice that received goat anti-TG3 produced papillary dermal immune deposits, and these deposits reacted with both rabbit anti-TG3 and DH patient sera. Three DH sera high in IgA anti-TG3 also produced deposits of granular IgA and TG3. We hypothesize that the IgA class anti-TG3 Abs are directly responsible for the immune deposits and that the TG3 is from human epidermis, as this is its only source in our model. These deposits seem to form over weeks in a process similar to an Ouchterlony immunodiffusion precipitate. This process of deposition explains the negative indirect immunofluorescence results with DH serum.
authors.affiliation: Department of Dermatology, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Zone
authors.forename: Linda A
authors.initials: LA
authors.lastname: Schmidt
authors.forename: Ted B
authors.initials: TB
authors.lastname: Taylor
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hull
authors.forename: Michael C
authors.initials: MC
authors.lastname: Sotiriou
authors.forename: Troy D
authors.initials: TD
authors.lastname: Jaskowski
authors.forename: Harry R
authors.initials: HR
authors.lastname: Hill
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Meyer
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001666:Binding Sites, Antibody / Q000276:immunology; D003238:Connective Tissue / Q000201:enzymology / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D003874:Dermatitis Herpetiformis / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D020405:Dermis / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006041:Goats; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D007070:Immunoglobulin A / Q000008:administration & dosage / Q000096:biosynthesis / Q000097:blood*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000096:biosynthesis / Q000097:blood*; D007271:Injections, Intradermal; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011817:Rabbits; D016038:Skin Transplantation / Q000276:immunology* / Q000473:pathology*; D011503:Transglutaminases / Q000097:blood / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C498712:TGM3 protein, human; D011503:Transglutaminases