{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:20:29Z","timestamp":1783405229719,"version":"3.54.6"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Pemphigus encompasses autoimmune blistering diseases driven by autoantibodies to desmosomal proteins. Disruption of keratinocyte adhesion produces acantholysis and epidermal fragility. Anti-CD20 B-cell depletion and IgG lowering strategies have transformed care, but many patients relapse, some variants respond incompletely, and durable drug-independent tolerance remains uncommon across variants. These gaps highlight that pemphigus is not a simple linear B-cell disorder, but an autoantibody disease sustained by a network linking the innate immunity, the adaptive lymphocytes, and the stromal niches. In this review, we focus on pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus\/paraneoplastic autoimmune multiorgan syndrome, and IgA pemphigus as representative variants within this network. We place these entities within a conceptual type 1, type 2, and type 3 immunity framework and summarize how central and peripheral B-cell tolerance can fail. We further consider current and emerging therapies as partial interventions within this network and outline next-generation strategies that modulate innate circuits, rewire survival pathways, restore antigen-specific regulation, and shift the adaptive autoimmune response toward a more tolerogenic state. Framing pemphigus in this way may help move the field from empiric immunosuppression toward precise immune engineering with the goal of durable immune reset and long-term drug-independent remission.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1844632","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:45:15Z","timestamp":1783403115000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling the autoimmune architecture of pemphigus: from B-cell depletion to network-based immune engineering"],"prefix":"10.3389","volume":"17","author":[{"given":"Pedram","family":"Shafiei-Jahani","sequence":"first","affiliation":[{"name":"David Geffen School of Medicine at University of California, Los Angeles (UCLA)","place":["Los Angeles, Los Angeles, CA, United States"]},{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine of University of Southern California 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