28.10.2021

ST18 affects cell-cell adhesion in pemphigus vulgaris in a TNFα-dependent fashion

S. Assaf [1, 2], L. Malki [1, 2], T. Mayer [1], J. Mohamad [1, 2], A. Peled [1, 2], M. Pavlovsky [1], K. Malovitski [1], O. Sarig [1], D. Vodo [1, 2], E. Sprecher [1, 2]. [1]Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; [2]Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Published JIMS Issue 08.05.2021
Background: Many procedures requiring sedation in the pediatric emergency department are performed by consultants from outside the department. This team usually includes orthopedic surgeons and general surgeons. As sedation is now a standard of care in such cases, we evaluated consultants' views on sedation.
Objectives: To evaluate consultants' views on sedation.
Methods: A questionnaire with both open-ended questions and Likert-type scores was distributed to all orthopedic surgeons and general surgeons performing procedures during the study period. The questionnaire was presented at three medical centers.
Results: The questionnaire was completed by 31 orthopedic surgeons and 16 general surgeons. Although the vast majority (93–100%) considered sedation important, a high percentage (64–75%) would still perform such procedures without sedation if not readily available.
Conclusions: Sedation is very important for patients and although consultants understand its importance, the emergency department staff must be vigilant in both being available and not allowing procedures to "escape" the use of sedation.

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.

 

References

1. Assaf S, Malki L, Mayer T, et al. ST18 affects cell–cell adhesion in pemphigus vulgaris in a tumour necrosis factor‐α‐dependent fashion. British Journal of Dermatology.

2. Sarig O, Bercovici S, Zoller L, et al. Population-specific association between a polymorphic variant in ST18, encoding a pro-apoptotic molecule, and pemphigus vulgaris. J Invest Dermatol. Jul 2012;132(7):1798-805. doi:10.1038/jid.2012.46

3. Vodo D, Sarig O, Geller S, et al. Identification of a Functional Risk Variant for Pemphigus Vulgaris in the ST18 Gene. PLoS Genet. May 2016;12(5):e1006008. doi:10.1371/journal.pgen.1006008

 

 

First published: 18 November 2020 https://doi.org/10.1111/bjd.19679