Premium
Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology
Author(s) -
Ahmed A. Razzaque,
Carrozzo Marco,
Caux Frédéric,
Cirillo Nicola,
Dmochowski Marian,
Alonso Agustín España,
Gniadecki Robert,
Hertl Michael,
LópezZabalza Maria J.,
Lotti Roberta,
Pincelli Carlo,
Pittelkow Mark,
Schmidt Enno,
Sinha Animesh A.,
Sprecher Eli,
Grando Sergei A.
Publication year - 2016
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13106
Subject(s) - autoantibody , pemphigus , pathophysiology , desmoglein , immunology , pathogenesis , desmoglein 1 , medicine , antibody , pathology
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 ( KC s) 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 KC s 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 KC s 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.