Pemphigus vulgaris (PV) is a life-threatening mucocutaneous autoimmune blistering disease. 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 in the tissue. Genetic variants in a gene called ST18 confer an increased risk of developing the disease². These genetic variants cause the skin cells to produce larger amounts of the ST18 protein which in turn leads to increased secretion of pro-inflammatory mediators (specifically the tumor necrosis factor-alpha -TNFα) and weakens the strength of the bonds between the cells. In a recent article the authors explored the mechanism through which ST18 contributes to the disruption of cell-cell adhesion³. Using several methods, they showed that ST18 directly activates the production of TNFα which impairs the stability of cell-cell adhesion, and thereby leads to blister formation. Indeed, when examining the skin of the patients themselves the authors show that affected individuals who carry the ST18 risk variant express higher amount of both ST18 and TNFα; these individuals also display a more extensive PV phenotype. Taken collectively, these observations point to TNFα’s role in the pathogenesis of PV associated with genetic variants in ST18. It is possible that genetic testing for ST18 may help predicting which PV patient is more likely to benefit from TNFα-blocking agents.

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