Year: 2025
Type: article
Abstract: Description Pemphigus is an autoimmune blistering disorder caused by autoantibodies against desmogleins (Dsg) 1 and 3, proteins essential for cell adhesion. Diagnosis relies on detecting tissue-bound autoantibodies. These antibodies disrupt cell adhesion, leading to blistering in skin or mucous membranes. While all IgG subclasses (IgG1, IgG2, IgG3, IgG4) are involved, IgG4 largely drives the response due to its unique Fab-arm exchange, making it monovalent and bispecific, unlike other IgGs that enhance crosslinking. This study isolated IgG subclasses from two pemphigus patients, examining their effects on keratinocytes (NHEK) at 0, 5, and 30 minutes. Multiplex kinome analyses showed that all IgG subclasses increased p38 MAPK signaling, linked to Dsg3 internalization, and activated kinases like PKC, CaMK4, and IKK-epsilon. MAP3K8 and mTOR/FRAP activities also rose under both IgG4 and IgG1-3 treatments, but only IgG4 uniquely increased CDK4, 6, 9, and 11. Confocal microscopy confirmed both IgG4 and IgG1-3 caused Dsg3 internalization. However, IgG4-treated keratinocytes showed no clustering, confirming subclass separation. This study highlights IgG subclass-specific kinase activation in pemphigus, especially the role of p38 MAPK and CDKs in IgG4-mediated Dsg3 internalization. Further research should explore subclass-specific signaling to identify kinase-targeted therapies for pemphigus. Topic Categories Basic Autoimmunity (BA)
Source: The Journal of Immunology
Institution: Catholic University of Korea
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416446983
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