Pemphigus vulgaris (PV) is a paradigm of autoimmune disease affecting intercellular adhesion. The mechanisms that lead to cell–cell detachment (acantholysis) have crucial therapeutic implications and are currently undergoing major scrutiny. The first part of this review focuses on the classical view of the pathogenesis of PV, which is dominated by the cell adhesion molecules of the desmosome, namely desmogleins (Dsgs). Cloning of the DSG3 gene, generation DSG3 knock-out mice and isolation of monoclonal anti-Dsg3 IgG have aided to clarify the pathogenic mechanisms of PV, which are in part dependent on the fate of desmosomal molecules. These include perturbation of the desmosomal network at the transcriptional, translational, and interaction level, kinase activation, proteinase-mediated degradation, and hyper-adhesion. By the use of PV models, translational research has in turn helped shed light into the basic structure, function, and dynamics of assembly of desmosomal cadherins. The combined efforts of basic and applied research has resulted in tremendous advance into the understanding of epidermal adhesion and helped debunk old myths on the supposedly unique role of desmogleins in the mechanisms of cell–cell detachment in PV.
Pemphigus foliaceus, the most common autoimmune skin condition in dogs and cats, is characterized by pustules, erosions, and crusts. In this article, we focus on the diagnosis and treatment of pemphigus foliaceus in dogs and cats.
The signs of an attack on keratinocyte adhesion structures are clinically evident. When the tight bonds between superficial keratinocytes are affected, it manifests as vesicles and pustules. When the tight bonds between basilar keratinocytes and the skin’s basement membrane are affected, it manifests as bullae (large blisters) and ulcers.
In pemphigus foliaceus in people, the most common target of autoantibodies is the desmoglein 1 (DSG1) glycoprotein in the desmosome. The autoantibody response primarily involves IgG (IgG4 subclass). Initial studies in dogs with pemphigus foliaceus only rarely detected an IgG autoantibody response, but more recent work using different substrates in indirect immunofluorescence testing confirms that IgG autoantibodies are important in canine pemphigus foliaceus. However, DSG1 is not commonly targeted in pemphigus foliaceus in dogs ; it is not yet known which part of the desmosome is targeted in most canine pemphigus foliaceus cases. Early immunoblotting studies revealed that the target was a 148 kDa or 160 kDa protein. Immunoelectron microscopy shows that the site of autoantibody binding is in the extracellular region of the desmosome.
Genetic factors can influence the development of pemphigus foliaceus. In dogs, it is more frequently diagnosed in two breeds with closely related genotypes, Akitas and chows. Pemphigus foliaceus has also been reported in littermates. No breed disposition has been noted in feline pemphigus foliaceus. Sex and age appear to be unrelated to the development of pemphigus foliaceus in dogs and cats. The age of onset is variable and ranges from 1 to 16 years in dogs and less than 1 year of age4 to up to 17 years of age in cats.