Despite the rising incidence of autoimmunity, therapeutic options for patients with autoimmune disease still rely on decades-old immunosuppressive strategies that risk severe and potentially fatal complications. Thus, novel therapeutic approaches for autoimmune diseases are greatly needed in order to minimize treatment-related toxicity. Such strategies would ideally target only the autoreactive immune components to preserve beneficial immunity. Here, we review how several decades of basic, translational, and clinical research on the immunology of pemphigus vulgaris (PV), an autoantibody-mediated skin disease, have enabled the development of targeted immunotherapeutic strategies. We discuss research to elucidate the pathophysiology of PV and how the knowledge afforded by these studies has led to the preclinical and clinical testing of targeted approaches to neutralize autoantibodies, to induce antigen-specific tolerance, and to specifically eliminate autoreactive B cells in PV.
Christoph T. Ellebrecht, Aimee S. Payne
Diagnosis of pemphigus vulgaris.
Wide-spread skin blisters and crusted erosions cause pain, itching, and risk of infection (top). Diagnosis of PV is based on histology, which shows a classic “row of tombstones,” representing loss of basal keratinocyte adhesion from suprabasal keratinocytes (bottom left), and immunofluorescence analysis of patient skin or serum samples, which documents binding of autoantibodies to the keratinocyte cell surface (bottom right). ×400 magnification for bottom panels.