Bullous pemphigoid (BP) is characterized by the deposition of IgG in the basement membrane zone, infiltration of eosinophils, and blister formation. The purpose of this study was to evaluate a potential role of IgE basement membrane antibodies in the histological findings of BP. LABD97 is a component of the shed ectodomain of bullous pemphigoid antigen 2. We have developed an IgE hybridoma to LABD97 antigen. This hybridoma was injected subcutaneously in SCID mice with engrafted human skin. A subcutaneous hybridoma secreting IgE antibodies developed. An IgE mouse hybridoma to trinitrophenyl was used as a control. Human grafts and mouse skin were examined grossly over 21 days, histologically, and immunopathologically at day 21 after injection of the hybridoma. A visible subcutaneous tumor developed in 10-14 days. Erythema and intense scratching developed 2-3 days before the tumor in test mice, but not in controls. At day 21, 16/16 test mice developed intense eosinophil infiltration and degranulation of the human mast cells within the grafts and 13/16 developed histological, but not clinically visible, basement membrane blisters. Human skin grafts of control mice and normal mouse skin on the test mice and control mice did not develop any histological abnormalities. IgE antibodies to LABD97 recapitulate the histological inflammatory process seen in BP.

IgA antibodies to TG3 are elevated in patients with DH and adults with CD. The progressive expansion of the epitope-binding profile of IgA antitransglutaminase antibodies in patients with CD may explain the development of DH in patients with undiagnosed CD during their adult life.

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.

Brown recluse spider (Loxosceles reclusa) venom phospholipase D (PLD) generates lysophosphatidic acid (LPA).