Pemphigus & Pemphigoid
- For many years, The Journal of Investigative Dermatology (JID) has been a leader in our understanding of many aspects of the major autoimmune blistering skin diseases, pemphigus and bullous pemphigoid. The purpose of this review is to highlight and summarize those advances by discussing the respective articles, published in the JID from 2015 to 2019. Seminal articles from elsewhere in the literature that set the stage for those advances, or that are “classics” in the area, are also included to provide context and a more complete picture.
- The study by Plaquevent et al. strongly supports the recent discovery that the use of gliptins is a risk factor for bullous pemphigoid (BP). However, regarding the phenotype of gliptin-associated BP and the necessity of gliptin withdrawal, clinical data remain scarce. We predict that future studies of gliptin-associated BP will offer valuable information concerning autoimmunity against BP180 and may also shed light on the pathology of autoimmune diseases in general.
- Bullous pemphigoid is an autoantibody-mediated skin blistering disease. Previous studies revealed that intravenous Ig is therapeutic in animal models of bullous pemphigoid by saturating the IgG-protective receptor FcRn, thereby accelerating degradation of pathogenic IgG. Sasaoka et al. demonstrate that the inhibitory effects of intravenous Ig on bullous pemphigoid are also associated with negative modulation of cytokine production by keratinocytes.
- Bullous pemphigoid is a potentially life-threatening autoantibody-mediated dermatosis characterized by blister formation. Experimental mouse models of bullous pemphigoid feature complement-induced inflammation and tissue damage. Kasprick et al. now provide preclinical data that utilize ex vivo human skin assays and support testing of complement inhibition as a therapeutic strategy in human bullous pemphigoid.
- Pemphigus vulgaris is an autoimmune blistering disease caused by anti-desmoglein 3 IgG autoantibodies. It is accepted that interactions between autoreactive B and T cells are key to humoral autoimmunity targeting desmoglein 3. This orchestrated process usually occurs in secondary lymphoid organs, including the spleen and lymph nodes. Thus, it seems likely that autoreactive B cells reside and produce autoantibodies in these tissues. Yuan et al. analyzed lymphocytes in the lesional skin of patients with pemphigus vulgaris using several experimental techniques and concluded that desmoglein 3-reactive B cells were present.
- Mice carrying a deletion in the NC14A domain of murine type XVII collagen begin scratching at age 2 months and then develop erosions, subepidermal vesicles, eosinophil-rich skin infiltrates, and autoantibodies directed against a 180 kDa skin protein that appears to be type XVII collagen. These mice represent a bullous pemphigoid animal model featuring pruritus in immunocompetent, mature, and largely unmanipulated animals.