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Exp Dermatol. 2016 Nov;25(11):839-846. doi: 10.1111/exd.13106.

Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology.

Author information

1
Department of Dermatology of Tufts University and Center for Blistering Diseases, Boston, MA, USA.
2
School of Dental Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
3
Department of Dermatology, University Paris 13, Avicenne Hospital, APHP, Bobigny, France.
4
Melbourne Dental School and Oral Health CRC, The University of Melbourne, Melbourne, Vic., Australia.
5
Autoimmune Blistering Dermatoses Section, Department of Dermatology, Poznan University of Medical Sciences, Poznan, Poland.
6
Department of Dermatology, School of Medicine, University Clinic of Navarra, University of Navarra, Navarra, Spain.
7
Division of Dermatology, University of Alberta, Edmonton, AB, Canada.
8
Department of Dermatology and Allergology, Philipps University, Marburg, Germany.
9
Department of Biochemistry and Genetics, University of Navarra, Navarra, Spain.
10
Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
11
Department of Dermatology, Mayo Clinic, Scottsdale, AZ, USA.
12
Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany.
13
Department of Dermatology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
14
Department of Dermatology, Tel Aviv Medical Center, Tel Aviv, Israel.
15
Institute for Immunology and Departments of Dermatology and Biological Chemistry, University of California, Irvine, CA, USA. sgrando@uci.edu.

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.

KEYWORDS:

FcRn; acantholysis; antimitochondrial antibody; autoantibody; autoantigen; autoimmunity; desmogleins 1 and 3; pemphigus vulgaris

PMID:
27305362
DOI:
10.1111/exd.13106
[Indexed for MEDLINE]

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