Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology
| Autor: | Animesh A. Sinha, Roberta Lotti, Nicola Cirillo, Michael Hertl, A. Razzaque Ahmed, Frédéric Caux, Agustín España Alonso, Enno Schmidt, María J. López-Zabalza, Robert Gniadecki, Carlo Pincelli, Marian Dmochowski, Marco Carrozzo, Sergei A. Grando, Eli Sprecher, Mark R. Pittelkow |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Antimitochondrial antibody Autoimmunity Dermatology Disease medicine.disease_cause Desmoglein Biochemistry Pathogenesis 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Autoantibody Autoantigen medicine Animals Humans Desmogleins 1 and 3 Molecular Biology integumentary system business.industry Acantholysis Pemphigus vulgaris medicine.disease Pemphigus FcRn 030104 developmental biology 2708 Immunology business Desmogleins |
| DOI: | 10.1111/(ISSN)1600-0625 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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