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- Title
Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology.
- Authors
Ahmed, A. Razzaque; Carrozzo, Marco; Caux, Frédéric; Cirillo, Nicola; Dmochowski, Marian; Alonso, Agustín España; Gniadecki, Robert; Hertl, Michael; López‐Zabalza, Maria J.; Lotti, Roberta; Pincelli, Carlo; Pittelkow, Mark; Schmidt, Enno; Sinha, Animesh A.; Sprecher, Eli; Grando, Sergei A.
- 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-Dsg-specific autoantibodies, and (iii) determine the extent of the contribution of non-Dsg antibodies in disease pathophysiology.
- Subjects
PEMPHIGUS; SKIN diseases; PATHOGENIC microorganisms; IMMUNOGLOBULINS; PATHOLOGICAL physiology
- Publication
Experimental Dermatology, 2016, Vol 25, Issue 11, p839
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/exd.13106