Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by cell–cell detachment (or acantholysis) and blister formation. While the signaling mechanisms that associate with skin/mucosal blistering are being elucidated, specific treatment strategies targeting PV‐specific pathomechanisms, particularly kinase signaling, have yet to be established. Hence, the aim of this review was to systematically evaluate molecules in the class of kinases that are essential for acantholysis and blister formation and are therefore candidates for targeted therapy. English articles from PubMed and Scopus databases were searched, and included in vitro, in vivo, and human studies that investigated the role of kinases in PV. We selected studies, extracted data and assessed risk of bias in duplicates and the results were reported according to the methodology outlined by the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA). The risk of bias assessment was performed on in vivo studies utilizing SYRCLE's risk of bias tool. Thirty‐five studies were included that satisfied the pathogenicity criterion of kinases in PV, the vast majority being experimental models that used PV sera (n = 13) and PV‐IgG (n = 22). Inhibition of kinase activity (p38MAPK, PKC, TK, c‐Src, EGFR, ERK, mTOR, BTK, and CDK2) was achieved mostly by pharmacological means. Overall, we found substantial evidence that kinase inhibition reduced PV‐associated phosphorylation events and keratinocyte disassociation, prevented acantholysis, and blocked blister formation. However, the scarce adherence to standardized reporting systems and the experimental protocols/models used did limit the internal and external validity of these studies. In summary, this systematic review highlighted the pathogenic intracellular events mediated by kinases in PV acantholysis and presented kinase signaling as a promising avenue for translational research. In particular, the molecules identified and discussed in this study represent potential candidates for the development of mechanism‐based interventions in PV.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.