Patients with pemphigus foliaceus (PF) have blisters on skin, but not mucous membranes, whereas patients with pemphigus vulgaris (PV) develop blisters on mucous membranes and/or skin. PF and PV blisters are due to loss of keratinocyte cell–cell adhesion in the superficial and deep epidermis, respectively. PF autoantibodies are directed against desmoglein (Dsg) 1; PV autoantibodies bind Dsg3 or both Dsg3 and Dsg1. In this study, we test the hypothesis that coexpression of Dsg1 and Dsg3 in keratinocytes protects against pathology due to antibody-induced dysfunction of either one alone. Using passive transfer of pemphigus IgG to normal and DSG3null neonatal mice, we show that in the areas of epidermis and mucous membrane that coexpress Dsg1 and Dsg3, antibodies against either desmoglein alone do not cause spontaneous blisters, but antibodies against both do. In areas (such as superficial epidermis of normal mice) where Dsg1 without Dsg3 is expressed, anti-Dsg1 antibodies alone can cause blisters. Thus, the anti-desmoglein antibody profiles in pemphigus sera and the normal tissue distributions of Dsg1 and Dsg3 determine the sites of blister formation. These studies suggest that pemphigus autoantibodies inhibit the adhesive function of desmoglein proteins, and demonstrate that either Dsg1 or Dsg3 alone is sufficient to maintain keratinocyte adhesion.
My G. Mahoney, Zhihong Wang, Kyle Rothenberger, Peter J. Koch, Masayuki Amagai, John R. Stanley
Title and authors | Publication | Year |
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Pemphigus IgG causes skin splitting in the presence of both desmoglein 1 and desmoglein 3
V Spindler, D Drenckhahn, D Zillikens, J Waschke |
The American Journal of Pathology | 2007 |
Pemphigus vulgaris immunoglobulin G can recognize a 130 000 MW antigen other than desmoglein 3 on peripheral blood mononuclear cell surface
N Cirillo, F Gombos, A Lanza |
Immunology | 2007 |
A Perspective of Pemphigus from Bedside and Laboratory-Bench
Y Kitajima, Y Aoyama |
Clinical Reviews in Allergy & Immunology | 2007 |
What’s new in blistering disorders?
P Chaudhari, MP Marinkovich |
Current Allergy and Asthma Reports | 2007 |
Imaging and Force Spectroscopy on Desmoglein 1 Using Atomic Force Microscopy Reveal Multivalent Ca2+-Dependent, Low-Affinity Trans-Interaction
J Waschke, C Menendez-Castro, P Bruggeman, R Koob, M Amagai, HJ Gruber, D Drenckhahn, W Baumgartner |
Journal of Membrane Biology | 2007 |
Mucocutaneous pemphigus vulgaris carrying high-titre antidesmoglein 1 antibodies with skin lesions resembling pemphigus erythematosus
N Cirillo, R Santoro, M Lanza, P Annese, F Gombos, A Lanza |
Clinical and Experimental Dermatology | 2007 |
IgG against extracellular subdomains of desmoglein 3 relates to clinical phenotype of pemphigus vulgaris
R Müller, V Svoboda, E Wenzel, HH Müller, M Hertl |
Experimental Dermatology | 2007 |
Beyond steric hindrance: The role of adhesion signaling pathways in the pathogenesis of pemphigus
P Sharma, X Mao, AS Payne |
Journal of Dermatological Science | 2007 |
If pemphigus vulgaris IgG are the cause of acantholysis, new IgG-independent mechanisms are the concause
N Cirillo, M Lanza, F Femiano, GM Gaeta, AD Rosa, F Gombos, A Lanza |
Journal of Cellular Physiology | 2007 |
Intraperitoneal injection of pemphigus vulgaris-IgG into mouse depletes epidermal keratinocytes of desmoglein 3 associated with generation of acantholysis
E Shu, Y Yamamoto, Y Aoyama, Y Kitajima |
Archives of Dermatological Research | 2007 |
No activation of urokinase plasminogen activator by anti-desmoglein 3 monoclonal IgG antibodies in cultured human keratinocytes
Y Yamamoto, Y Aoyama, E Shu, K Tsunoda, M Amagai, Y Kitajima |
Journal of Dermatological Science | 2007 |
Pemphigus vulgaris presenting in a radiation portal
AC Robbins, Z Lazarova, MM Janson, JA Fairley |
Journal of the American Academy of Dermatology | 2007 |
Caspase-dependent cleavage of desmoglein 1 depends on the apoptotic stimulus
A Lanza, N Cirillo |
British Journal of Dermatology | 2007 |
Metalloproteinase 9 is the outer executioner of desmoglein 3 in apoptotic keratinocytes
N Cirillo, F Femiano, F Gombos, A Lanza |
Oral Diseases | 2007 |
IgG autoantibodies directed against desmoglein 3 cause dissociation of keratinocytes in canine pemphigus vulgaris and paraneoplastic pemphigus
K Nishifuji, T Olivry, K Ishii, T Iwasaki, M Amagai |
Veterinary Immunology and Immunopathology | 2007 |
Using Desmoglein 1 and 3 Enzyme-linked Immunosorbent Assay as an Adjunct Diagnostic Tool for Pemphigus
CH Huang, CC Chen, CJ Wang, YT Chang, HN Liu |
Journal of the Chinese Medical Association | 2007 |
Internalization of Non-Clustered Desmoglein 1 without Depletion of Desmoglein 1 from Adhesion Complexes in An Experimental Model of the Autoimmune Disease Pemphigus Foliaceus
A Lanza, AD Rosa, F Femiano, P Annese, E Ruocco, F Gombos, M Lanza, N Cirillo |
International journal of immunopathology and pharmacology | 2007 |
Anti-desmoglein 3 (Dsg3) Monoclonal Antibodies Deplete Desmosomes of Dsg3 and Differ in Their Dsg3-depleting Activities Related to Pathogenicity
Y Yamamoto, Y Aoyama, E Shu, K Tsunoda, M Amagai, Y Kitajima |
The Journal of biological chemistry | 2007 |