Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology

A. Razzaque Ahmed, Marco Carrozzo, Frédéric Caux, Nicola Cirillo, Marian Dmochowski, Agustín España Alonso, Robert Gniadecki, Michael Hertl, Maria J. López-Zabalza, Roberta Lotti, Carlo Pincelli, Mark Pittelkow, Enno Schmidt, Animesh A. Sinha, Eli Sprecher, Sergei A. Grando

Research output: Contribution to journalArticlepeer-review

Abstract

This viewpoint highlights major, partly controversial concepts about the pathogenesis of pemphigus. The monopathogenic theory explains intra-epidermal blistering through the “desmoglein (Dsg) compensation” hypothesis, according to which an antibody-dependent disabling of Dsg 1-and/ or Dsg 3-mediated cell-cell attachments of keratinocytes (KCs) is sufficient to disrupt epidermal integrity and cause blistering. The multipathogenic theory explains intra-epidermal blistering through the “multiple hit” hypothesis stating that a simultaneous and synchronized inactivation of the physiological mechanisms regulating and/or mediating intercellular adhesion of KCs is necessary to disrupt epidermal integrity. The major premise for a multipathogenic theory is that a single type of autoantibody induces only reversible changes, so that affected KCs can recover due to a self-repair. The damage, however, becomes irreversible when the salvage pathway and/or other cell functions are altered by a partnering autoantibody and/or other pathogenic factors. Future studies are needed to (i) corroborate these findings, (ii) characterize in detail patient populations with non-Dsgspecific autoantibodies, and (iii) determine the extent of the contribution of non-Dsg antibodies in disease pathophysiology.

Original languageEnglish
Pages (from-to)839-846
Number of pages8
JournalExperimental Dermatology
Volume25
Issue number11
DOIs
StatePublished - 1 Nov 2016
Externally publishedYes

Keywords

  • Acantholysis
  • Antimitochondrial antibody
  • Autoantibody
  • Autoantigen
  • Autoimmunity
  • Desmogleins 1 and 3
  • FcRn
  • Pemphigus vulgaris

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