Genetic studies point to novel therapeutic targets in pemphigus vulgaris

Abstract

British Journal of DermatologyVolume 184, Issue 6 p. e209-e209 Plain Language SummaryFree Access Genetic studies point to novel therapeutic targets in pemphigus vulgaris First published: 06 June 2021 https://doi.org/10.1111/bjd.20113AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract Linked Article: Assaf et al. Br J Dermatol 2021; 184:1153–1160. Pemphigus vulgaris (PV) is a life-threatening disease that may cause severe blistering of the skin and the mucous membranes lining the mouth, nose, throat, eyes and genital area. The blisters develop in the skin as a result of the formation of autoantibodies against proteins that are responsible for the attachment of the cells to each other (cell–cell adhesion) in the tissue. We previously discovered that genetic variants in a gene called ST18 resulted in an increased risk of developing the disease. We found that the genetic variants cause the skin cells to produce larger amounts of the ST18 protein, which in turn leads to increased secretion of proinflammatory mediators (specifically tumour necrosis factor-alpha, TNF-α) and weakens the strength of the bonds between the cells. Therefore, we set out to explore the mechanism through which ST18 contributes to the disruption of cell–cell adhesion. Using several methods, we showed that ST18 directly activates the production of TNF-α, which impairs the stability of cell–cell adhesion, and thereby leads to blister formation. We then looked at the skin of the patients themselves and found out that affected individuals who carry the ST18 risk variant express a higher amount of both ST18 and TNF-α; these individuals also have more extensive disease. Taken collectively, these observations point to TNF-α’s role in the development of PV associated with genetic variants in ST18. It is possible that genetic testing for ST18 may help in predicting which patients with PV are more likely to benefit from treatment with TNF-α-blocking agents. Volume184, Issue6June 2021Pages e209-e209 RelatedInformation