IgE Basement Membrane Zone Antibodies Induce Eosinophil Infiltration and Histological Blisters in Engrafted Human Skin on SCID Mice

Abstract

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.