Desmoglein 1 and Desmoglein 3 Are the Target Autoantigens in Herpetiform Pemphigus

Ishii, Ken; Amagai, Masayuki; Komai, Ayako; Ebihara, Tamotsu; Chorzelski, Tadeusz P.; Jabłońska, Stefania; Ohya, Kazuhiko; Nishikawa, Takeji; Hashimoto, Takashi

doi:10.1001/archderm.135.8.943

Cited by 80 publications

(69 citation statements)

References 23 publications

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“…The PH variant is clinically characterized by clusters of vesicles and occasionally pustules in the erythematous areas similar to those observed in dermatitis herpetiformis (Kasperkiewicz et al, 2014). This type of pemphigus demonstrates characteristic histological features, that is, eosinophilic spongiosis and micro-abscesses in the mid-or subcorneal epidermis with minimum acantholytic changes, despite the immunologically common features of anti-Dsg1 and/or Dsg3 antibodies (Ishii et al, 1999). A clinically and histologically unique variant, PVeg, is characterized by hypertrophic vegetations in the fl exures such as axillae, the groin, and the umbilicus, associated occasionally with pustules at the edge of the lesions with vegetations.…”

Section: Pemphigus As a Desmosome Remodeling Diseasementioning

confidence: 93%

150^thAnniversary Series: Desmosomes and Autoimmune Disease, Perspective of Dynamic Desmosome Remodeling and Its Impairments in Pemphigus

Kitajima

2014

Cell Communication & Adhesion

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Desmosomes are the most important intercellular adhering junctions that adhere two adjacent keratinocytes directly with desmosomal cadherins, that is, desmogleins (Dsgs) and desmocollins, forming an epidermal sheet. Recently, two cell -cell adhesion states of desmosomes, that is, " stable hyper-adhesion " and " dynamic weak-adhesion " conditions have been recognized. They are mutually reversible through cell signaling events involving protein kinase C (PKC), Src and epidermal growth factor receptor (EGFR) during Ca 2 ϩ -switching and wound healing. This remodeling is impaired in pemphigus vulgaris (PV, an autoimmune blistering disease), caused by anti-Dsg3 antibodies. The antibody binding to Dsg3 activates PKC, Src and EGFR, linked to generation of dynamic weak-adhesion desmosomes, followed by p38MAPK-mediated endocytosis of Dsg3, resulting in the specifi c depletion of Dsg3 from desmosomes and acantholysis. A variety of pemphigus outside-in signaling may explain different clinical (non-infl ammatory, infl ammatory, and necrolytic) types of pemphigus. Pemphigus could be referred to a " desmosome-remodeling disease involving pemphigus IgG-activated outside-in signaling events " .

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Section: Pemphigus As a Desmosome Remodeling Diseasementioning

confidence: 93%

150^thAnniversary Series: Desmosomes and Autoimmune Disease, Perspective of Dynamic Desmosome Remodeling and Its Impairments in Pemphigus

Kitajima

2014

Cell Communication & Adhesion

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“…As noted by Amagai et al [2, 4]and Ishii et al [15], pemphigus sera react with the epidermal cadherins Dsg1 and Dsg3. Most pemphigus patients have one of these antibodies or both.…”

Section: Discussionmentioning

confidence: 87%

“…We examined the circulating antibodies to Dsg1 and Dsg3 with an ELISA kit (MBL, Medical and Biological Laboratories Co. Ltd., Nagoya, Japan) using human Dsg1 and Dsg3 produced by the baculovirus expression system according to previously described methods [2, 4, 15]. …”

Section: Methodsmentioning

confidence: 99%

Antidesmoglein Autoantibodies in Silicosis Patients with No Bullous Diseases

Ueki¹,

Kohda²,

Nobutoh³

et al. 2001

Dermatology

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Background: Pemphigus is an autoimmune bullous disease characterized by the presence of antidesmoglein autoantibodies. However, the mechanism of its autoantibody production remains unknown. In previous reports, we have described rare cases of pemphigus and pemphigoid associated with silicosis. It is well known that during long-term silicosis, some autoimmune diseases, such as systemic sclerosis, systemic lupus erythematosus or rheumatoid arthritis, can occur. Objective: The aim of this study was to explore the presence of pemphigus or pemphigoid autoantibodies in silicosis patients without clinical bullous diseases or collagen diseases. Method: The presence of pemphigus antibodies was examined in 54 silicosis patients with no associated bullous diseases, using immunofluorescence, the enzyme-linked immunosorbent assay (ELISA) for desmoglein 1 and 3, and immunoblotting methods. In the antibody-positive cases, HLA genotyping of peripheral lymphocytes was performed with PCR-RFLP. Results: Seven out of the 54 patients were found to be positive for pemphigus antibodies and 1 for bullous pemphigoid by immunofluorescence. In addition, by ELISA, 6 patients were found to be positive against the desmoglein 1 antigen, 2 against the desmoglein 3 antigen and 2 against both desmoglein 1 and desmoglein 3. Conclusion: The results of the present study strongly suggest the occurrence of pemphigus and pemphigoid autoantibodies in patients with silicosis. It remains unclear whether such patients will develop an autoimmune bullous disease in the future. Accordingly, long-term follow-up of antibody-positive patients is required.

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“…They reported that 16 of 20 cases in HP serum samples contained anti-Dsg1 antibodies, and four cases contained anti-Dsg3 antibodies. 9 Regarding the cause of the different clinical presentation between HP and classical pemphigus in spite of the same target antigens, Ishii et al 9 suggested that autoantibodies in HP may recognize a functionally less important part of the molecule and therefore are not able to induce loss of cell adhesion. These autoantibodies may be sufficient to cause some inflammatory processes through complement activation or induction of cytokine release by keratinocytes, leading to intercellular edema and eosinophilic spongiosis.…”

Section: Discussionmentioning

confidence: 99%

Herpetiform pemphigus without anti‐desmoglein 1/3 autoantibodies

Nakashima

Fujimoto

Watanabe

et al. 2010

The Journal of Dermatology

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We report a patient with herpetiform pemphigus who was negative for autoantibodies to desmoglein (Dsg)1 or 3. He had erythemas with vesicles lining the margins on the trunk and extremities. Histopathology revealed intraepidermal blister with prominent eosinophil infiltration. Direct and indirect immunofluorescence demonstrated the presence of depositing and circulating immunoglobulin (Ig)G autoantibodies, but no IgA antibodies, to keratinocyte cell surface. Nonetheless, neither anti-Dsg1 nor Dsg3 antibodies were detected by enzyme-linked immunosorbent assay. Immunoblotting using human epidermal extracts also showed no reactivity with known intraepidermal or epidermaldermal junctional substances. Immunoelectronmicroscopy revealed the reactivity on the portion of keratinocyte cell surface but not on the desmosomes. This case suggests that non-desmoglein antigen on keratinocyte cell surface can be targeted in some patients with this unusual variant of pemphigus.

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Desmoglein 1 and Desmoglein 3 Are the Target Autoantigens in Herpetiform Pemphigus

Cited by 80 publications

References 23 publications

150^thAnniversary Series: Desmosomes and Autoimmune Disease, Perspective of Dynamic Desmosome Remodeling and Its Impairments in Pemphigus

150^thAnniversary Series: Desmosomes and Autoimmune Disease, Perspective of Dynamic Desmosome Remodeling and Its Impairments in Pemphigus

Antidesmoglein Autoantibodies in Silicosis Patients with No Bullous Diseases

Herpetiform pemphigus without anti‐desmoglein 1/3 autoantibodies

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Desmoglein 1 and Desmoglein 3 Are the Target Autoantigens in Herpetiform Pemphigus

Cited by 80 publications

References 23 publications

150thAnniversary Series: Desmosomes and Autoimmune Disease, Perspective of Dynamic Desmosome Remodeling and Its Impairments in Pemphigus

150thAnniversary Series: Desmosomes and Autoimmune Disease, Perspective of Dynamic Desmosome Remodeling and Its Impairments in Pemphigus

Antidesmoglein Autoantibodies in Silicosis Patients with No Bullous Diseases

Herpetiform pemphigus without anti‐desmoglein 1/3 autoantibodies

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150^thAnniversary Series: Desmosomes and Autoimmune Disease, Perspective of Dynamic Desmosome Remodeling and Its Impairments in Pemphigus

150^thAnniversary Series: Desmosomes and Autoimmune Disease, Perspective of Dynamic Desmosome Remodeling and Its Impairments in Pemphigus