In Pemphigus, Cell Detachment, Not Autoantibody Binding, Induces Cell-Wide, Long-Lasting Transcriptomic and Proteomic Changes

    February 2025 in “ bioRxiv (Cold Spring Harbor Laboratory) ”
    Veronika Hartmann, Sen Guo, Siavash Rahimi, Uta Katharina Radine, Danielle Malheiros, Amanda Salviano‐Silva, Valéria Bumiller‐Bini, Gabriel Adelman Cipolla, Verónica Calonga‐Solís, Axel Künstner, Imke A. K. Burmester, Ralf J. Ludwig, William V. J. Hariton, Christoph M. Hammers, Eike Müller, Hauke Busch, Jennifer E. Hundt
    TLDR Cell detachment, not autoantibody binding, causes major changes in pemphigus.
    This study investigates the molecular events following autoantibody binding in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) using human skin organ culture and 2D cell-culture models. The research found that autoantibody binding to desmoglein 1 and 3 does not directly induce significant transcriptomic or proteomic changes. Instead, these changes are secondary effects resulting from keratinocyte detachment and mechanical-stress-induced split formation. Split formation, observed as early as 5 hours post-injection, led to significant upregulation of IFNγ and TNFα-related genes, mediated by NFκB, MAPK, and JAK-STAT pathways. These findings suggest that the observed molecular changes are linked to reduced adhesion and mechanical stress rather than direct autoantibody action.
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