Journal of Autoimmunity (2001) 16, 411–421 doi:10.1006/jaut.2001.0510, available online at http://www.idealibrary.com on A Spontaneous Canine Model of Mucous Membrane (Cicatricial) Pemphigoid, an Autoimmune Blistering Disease Affecting Mucosae and Mucocutaneous Junctions Thierry Olivry 1 , Stanley M. Dunston 1 , Marianne Schachter 3 , Luting Xu 3 , Ngon Nguyen 2 , M. Peter Marinkovich 2 and Lawrence S. Chan 3 1 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA 2 Dermatology Service, VA Palo Alto Health Care System, Program in Epithelial Biology and Department of Dermatology, School of Medicine, Stanford University, Palo Alto, California, USA 3 Department of Dermatology, School of Medicine, Northwestern University, Chicago, Illinois, USA Received 17 October 2000 Accepted 24 January 2001 Key words: basement membrane, cicatricial, dog, skin Mucous membrane pemphigoid (MMP) is a rare autoimmune blistering dermatosis of humans that was previously known as cicatricial pemphigoid. It is characterized by vesicles, ulcers and scarring that affect predominantly mucosae and mucocutaneous junctions. Circulating autoantibodies recognize epitopes on basement membrane proteins such as collagen XVII or laminin- 5/6. Herein, we describe the clinico-pathological and immunological characteristics of 17 dogs afflicted with a dermatosis homologous to MMP of humans. Patients exhibited vesicles and erosions predominantly on mucous membranes or mucocutaneous junctions of the mouth, nose, eyes, genitalia or anus. Histopathology revealed subepithelial vesicles with variable dermal inflammation. Direct immunofluorescence demonstrated IgG or complement at the dermoepithelial junction. Indirect immunofluorescence using salt-split epithelia permitted the detection of circulating basement membrane-specific IgG autoantibodies in 15 cases. In 11 patients, autoantibodies recognized the NC16A segment of collagen XVII, as determined by salt-split indirect immunofluorescence, immunoblotting using canine keratinocytes and ELISA with synthetic canine peptides. In one dog, autoantiodies bound to the dermal side of salt-split epithelia and recognized epitopes within the 30 kDa carboxy- terminal segment of human collagen XVII. Canine MMP, like its human counterpart, exhibits distinctive clinical signs and histopathological lesions, yet circulating autoantibodies target different antigenic epitopes. This spontaneous canine model of MMP could prove useful for studies on the pathogenesis or therapy of this human disease. © 2001 Academic Press Introduction In human patients, skin blistering frequently occurs because of defective adhesion between epidermal cells or within the epidermal basement membrane zone [1]. Intra-epidermal or subepidermal vesiculation can develop because of mutations of genes encoding attachment proteins or due to the production of autoantibodies interfering with cell–cell or cell–matrix cohesion [2]. At this time, autoimmune subepidermal blistering diseases (AISBD) are subdivided based on clinical signs and identification of targeted autoanti- gens within the epidermal basement membrane [2]. Cicatricial pemphigoid (CP) is a rare autoimmune dermatosis of humans that is unique because of its phenotype and immunological characteristics. Indeed, vesicular and erosive lesions of CP exhibit a marked predilection for mucous membranes (e.g. oral cavity and conjunctiva) yet circulating autoantibodies target many different basement membrane antigens that include type XVII collagen (BP180, BPAG2) and laminin-5/6 [3, 4]. Because of the preponderance of mucosal lesions and the lack of cicatrix (scarring) in some patients with CP, there is a recent international consensus to rename this entity as ‘mucous membrane pemphigoid’ or (MMP) [L.S. Chan et al., unpublished]. In the dog, cutaneous blistering can arise also as a result of autoantibody targeting basement membrane adhesion proteins [5]. Dogs with skin vesiculation and basement-membrane specific autoantibodies first were reported 25 years ago [6, 7]. Yet, it is only with the recent availability of advanced immunological methods that the nosology of canine AISBD has been Correspondence to: Thierry Olivry, DrVet, PhD, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606. Fax: (919) 513-6336. E-mail: Thierry – Olivry@ncsu.edu 411 0896–8411/01/040411+11 $35.00/0 © 2001 Academic Press