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Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology

Lookup NU author(s): Professor Marco Carrozzo



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


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.

Publication metadata

Author(s): Ahmed AR, Carrozzo M, Caux F, Cirillo N, Dmochowski M, Alonso AE, Gniadecki R, Hertl M, Lopez-Zabalza MJ, Lotti R, Pincelli C, Pittelkow M, Schmidt E, Sinha AA, Sprecher E, Grando SA

Publication type: Article

Publication status: Published

Journal: Experimental Dermatology

Year: 2016

Volume: 25

Issue: 11

Pages: 839-846

Print publication date: 01/11/2016

Online publication date: 28/10/2016

Acceptance date: 02/06/2016

Date deposited: 30/03/2017

ISSN (print): 0906-6705

ISSN (electronic): 1600-0625

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/exd.13106


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