HYBRID EVENT: You can participate in person at Rome, Italy or Virtually from your home or work.
Sergei A Grando, Speaker at Cosmetology Meetings
University of California Irvine, United States
Title : Autoimmune pemphigus: Breakthrough discoveries in the pathophysiology and development of potentially curative treatment

Abstract:

Pemphigus vulgaris (PV) is an autoimmune blistering skin disease where autoantibody-mediated suprabasilar intraepidermal splitting causes flaccid blisters and non-healing erosions of the oral mucosa and sometimes also of the skin. Historically, acantholysis in PV was thought to be driven by anti-desmoglein (Dsg) antibodies. Herein, we describe the role of autoantibodies against keratinocyte muscarinic and nicotinic acetylcholine receptors in the immunopathogenesis of PV. The identification of targets in this disease is important, as they may lead to novel diagnostic and therapeutic options in the future for this potentially deadly disease. Treatment of PV patients with the novel multidrug protocol consisting of a short course of prednisone and a long-term maintenance therapy with intravenous immunoglobulin (IVIg) paired with a cytotoxic immunosuppressive drug as well as a tetracycline derivative and niacinamide, led to a stable remission off drugs for longer than 5 years in 88% of patients. This is superior to the treatment outcome of the FDA-approved regimen combining short-term prednisone with rituximab, because 32% of pemphigus patients who were in clinical remission off therapy relapsed within 5 years after treatment. The superiority of the multidrug protocol is based on the additive/synergistic effects of individual treatment modalities that target specific aspects of PV immunopathology, such as: 1) protection of keratinocytes from autoantibody attack by systemic corticosteroids and mitochondrion-protecting drugs, 2) selective elimination of autoantibodies by IVIg and 3) prevention of autoantibody production by a cytotoxic immunosuppressive drug.

Audience Take Away Notes :

  • Corticosteroids increase resistance of keratinocytes to the acantholytic action of pemphigus autoantibodies by increasing their cell adhesive properties
  • A combination of doxycycline or minocycline with niacinamide (a.k.a. nicotinamide) protects keratinocytes from anti-mitochondrion antibodies
  • IVIg provides for selective elimination of pathogenic IgGs due to saturation of FcRn and replenishment of non-pathogenic IgGs
  • Combining IVIg with of a cytotoxic immunosuppressive drug can prevent the rebound effect
  • The multidrug protocol for potentially curative treatment of pemphigus allows a lower relapse rate, compared to that of the FDA-approved prednisone/rituximab treatment regimen

Biography:

Sergei A. Grando, M.D., Ph.D., D.Sci., is Distinguished Professor of Dermatology at the University of California Irvine. He graduated from Kyiv Medical Institute in 1980, obtained his Ph.D. in 1984 and in 1989, the Doctor of Science in medicine (D.Sci.) degree for studies of pemphigus and pemphigoid. From 1991 to 1996 was at University of Minnesota, from 1996 to 2007 at University of California Davis, and then joined UC Irvine. He is certified by the American Board of Dermatology. He has published 285 papers and obtained over $12 million research funding from NIH and other funding agencies in the USA.

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