The epithelia of the skin and oral mucosa are comprised of multiple layers of cells. A key difference between the skin and oral mucosa is that the skin has a thick layer of dead keratinocytes, the stratum corneum, that functions as a protective barrier against pathogens and dehydration.1
Buccal mucosa
In the epidermis of normal healthy skin and mucosal membranes, cells are bound to each other by desmosomes and to the extracellular matrix by hemidesmosomes. Cell-cell adhesion in the desmosomes is facilitated by desmoglein proteins that form bonds between neighboring epithelial cells.2
Figure adapted with permission from Kasperkiewicz M, et al. Nat Rev Dis Primers. 2017;3:17026.
PV is an autoimmune disease and caused by the development of immunoglobulin G (IgG) antibodies against the extracellular domains of desmogleins, specifically desmoglein 1 (DSG1) and desmoglein 3 (DSG3).3 B cells play a significant pathophysiological role in PV, as antibodies are produced by B cells as part of the adaptive immune response, including the production of autoantibodies in PV (anti-DSG3 and anti-DSG1)3. The autoantibodies to DSG1 and DSG3 disrupt the DSG-mediated binding between epithelial cells driving the loss of cell-cell adhesions between keratinocytes, a process known as acantholysis. It is as a result of acantholysis that severe blisters develop on the skin and/or mucosal membranes.3
Anti-DSG antibodies are hypothesized to result in acantholysis through two mechanisms: (1) auto-antibody-mediated steric hindrance of desmosomal adhesion and/or interference with desmosome assembly, and (2) intracellular cell signaling pathways that augment the autoimmune response.3
Figure adapted with permission from Kasperkiewicz M, et al. Nat Rev Dis Primers. 2017;3:17026.
DSG1 and DSG3 are expressed differently in the skin and mucous membranes. DSG3 is expressed more highly than DSG1 in the mucous membranes. In the skin, DSG1 is expressed in the spinous and granular layers and is more abundant than DSG3, which is limited to the basal layers.3
In patients with PV, blisters arise in layers corresponding with the locations of DSG1 or DSG3 in the skin or mucosa. PV can be further subdivided into mucosal-dominant, mucocutaenous or cutaneous type.3 The cutaneous form is less common than the other forms which also involve the mucosal membranes.3
To learn more about the pathophysiology of PV, please watch the video
This website is a non-promotional global resource intended to facilitate transparent scientific exchange regarding developments in medical research, diagnostics, and disease management. It is intended for healthcare professionals.
Not a healthcare professional? Browse:
This global website is intended for healthcare professionals outside the UK, US, Canada and Australia. The content on this website may include scientific information about experimental or investigational compounds, indications and services that are not approved or valid in your jurisdiction. Registration status and prescribing information of medicinal products may differ between countries. Please refer to local product information for any medicinal products mentioned on this website. Information available on this website does not constitute professional medical advice, and Roche and Genentech accept no responsibility for access to or use of the same.
You are Leaving Medically
By following this link, you are leaving Roche Website and entering a site that is not owned or controlled by Roche. Roche does not take any responsibility for acces to or use of this website, nor for any content therein.
You are Leaving the Global Medically Site
By following this link, you are being redirected to another Roche page.