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Seminars in Immunopathology
Published in: Seminars in Immunopathology 1/2016

01-01-2016 | Review

Immune response in pemphigus and beyond: progresses and emerging concepts

Authors: Giovanni Di Zenzo, Kyle T. Amber, Beyza S. Sayar, Eliane J. Müller, Luca Borradori

Published in: Seminars in Immunopathology | Issue 1/2016

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Abstract

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two severe autoimmune bullous diseases of the mucosae and/or skin associated with autoantibodies directed against desmoglein (Dsg) 3 and/or Dsg1. These two desmosomal cadherins, typifying stratified epithelia, are components of cell adhesion complexes called desmosomes and represent extra-desmosomal adhesion receptors. We herein review the advances in our understanding of the immune response underlying pemphigus, including human leucocyte antigen (HLA) class II-associated genetic susceptibility, characteristics of pathogenic anti-Dsg antibodies, antigenic mapping studies as well as findings about Dsg-specific B and T cells. The pathogenicity of anti-Dsg autoantibodies has been convincingly demonstrated. Disease activity and clinical phenotype correlate with anti-Dsg antibody titers and profile while passive transfer of anti-Dsg IgG from pemphigus patients’ results in pemphigus-like lesions in neonatal and adult mice. Finally, adoptive transfer of splenocytes from Dsg3-knockout mice immunized with murine Dsg3 into immunodeficient mice phenotypically recapitulates PV. Although the exact pathogenic mechanisms leading to blister formation have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation, at least for PV. These new insights not only highlight the key role of Dsgs in maintenance of tissue homeostasis but are expected to progressively change pemphigus management, paving the way for novel targeted immunologic and pharmacologic therapies.
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Metadata
Title
Immune response in pemphigus and beyond: progresses and emerging concepts
Authors
Giovanni Di Zenzo
Kyle T. Amber
Beyza S. Sayar
Eliane J. Müller
Luca Borradori
Publication date
01-01-2016
Publisher
Springer Berlin Heidelberg
Published in
Seminars in Immunopathology / Issue 1/2016
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-015-0541-1

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