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.

Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology / Ahmed, A. Razzaque; Carrozzo, Marco; Caux, Frã©dã©ric; Cirillo, Nicola; Dmochowski, Marian; Alonso, Agustã­n Espaã±a; Gniadecki, Robert; Hertl, Michael; Lã³pez-zabalza, Maria J.; Lotti, Roberta; Pincelli, Carlo; Pittelkow, Mark; Schmidt, Enno; Sinha, Animesh A.; Sprecher, Eli; Grando, Sergei A.. - In: EXPERIMENTAL DERMATOLOGY. - ISSN 0906-6705. - 25:11(2016), pp. 839-846. [10.1111/exd.13106]

Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology

Lotti, Roberta;Pincelli, Carlo;
2016

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.
25
11
839
846
Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology / Ahmed, A. Razzaque; Carrozzo, Marco; Caux, Frã©dã©ric; Cirillo, Nicola; Dmochowski, Marian; Alonso, Agustã­n Espaã±a; Gniadecki, Robert; Hertl, Michael; Lã³pez-zabalza, Maria J.; Lotti, Roberta; Pincelli, Carlo; Pittelkow, Mark; Schmidt, Enno; Sinha, Animesh A.; Sprecher, Eli; Grando, Sergei A.. - In: EXPERIMENTAL DERMATOLOGY. - ISSN 0906-6705. - 25:11(2016), pp. 839-846. [10.1111/exd.13106]
Ahmed, A. Razzaque; Carrozzo, Marco; Caux, Frã©dã©ric; Cirillo, Nicola; Dmochowski, Marian; Alonso, Agustã­n Espaã±a; Gniadecki, Robert; Hertl, Michael; Lã³pez-zabalza, Maria J.; Lotti, Roberta; Pincelli, Carlo; Pittelkow, Mark; Schmidt, Enno; Sinha, Animesh A.; Sprecher, Eli; Grando, Sergei A.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1147549
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