Altered Immunohistochemical Staining for Desmoglein in Skin Biopsies in Canine Pemphigus Foliaceus

Steeves, Elizabeth B.; Chelack, Brian J.; Clark, Edward G.; Haines, Deborah M.

doi:10.1177/104063870201400110

Cited by 10 publications

(12 citation statements)

References 9 publications

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“…autoimmune) pemphigus (14%) was not seen in our patients, 28 and nearly all dogs with PAPLR and AIPF had abnormal lesional DSG1 staining, like humans with idiopathic pemphigus 28 . This observation again supports the similarity of PAPLR and canine AIPF 27 …”

Section: Discussionsupporting

confidence: 84%

“…Skin lesions of autoimmune canine or human pemphigus variants are often associated with the redistribution of desmosomal cadherin adhesion molecules, which can be seen as either ‘dotted’ or ‘patchy’ patterns on DSG1 immunostains 27,28 . Remarkably, these abnormal patterns are seen less commonly in cases of human drug‐induced pemphigus, in which a normal intercellular ‘fishnet’ fluorescence is seen more commonly 28 .…”

Section: Methodsmentioning

confidence: 99%

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Metaflumizone–amitraz (Promeris)‐associated pustular acantholytic dermatitis in 22 dogs: evidence suggests contact drug‐triggered pemphigus foliaceus

Oberkirchner¹,

Linder

Dunston³

et al. 2011

Veterinary Dermatology

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Promeris Duo (PD) is a novel topical flea and tick preventative for dogs, which is also licensed for treatment of canine demodicosis. In this article, we present 22 dogs that all developed pemphigus foliaceus (PF)-like cutaneous drug reactions at the site of PD application. In eight dogs, the lesions were restricted to the application site (localized group). Signs of systemic illness were reported in three dogs, and four required immunosuppressive treatment. Direct immunofluorescence for IgG was positive in four dogs, although circulating antikeratinocyte IgG could not be detected in any tested sera. Complete remission was achieved in all dogs, with one patient still remaining on treatment. Fourteen dogs developed skin lesions at the application site as well as other noncontiguous areas (distant group). Systemic signs were reported in 11 dogs, and immunosuppression was required in 10 cases. Direct and indirect immunofluorescence tests were positive for antikeratinocyte autoantibodies in 10 of 13 and six of 10 patients with distant disease, respectively. Complete remission was achieved in 10 of 13 dogs with distant disease; one-third are still on treatment. Histological changes were similar to canine PF. Desmosomal architectural changes, assessed by desmoglein-1 immunostaining, were also similar to those of dogs with spontaneous autoimmune PF. Apoptosis did not appear to contribute to lesion formation, in either autoimmune or PD-associated PF. In conclusion, PD has the potential of triggering a variant of PF that resembles spontaneously occurring autoimmune PF at clinical, morphological, immunological and treatment outcome levels.

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Section: Discussionsupporting

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Metaflumizone–amitraz (Promeris)‐associated pustular acantholytic dermatitis in 22 dogs: evidence suggests contact drug‐triggered pemphigus foliaceus

Oberkirchner¹,

Linder

Dunston³

et al. 2011

Veterinary Dermatology

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“…Interestingly, the pattern of Dsg1 internalization observed in our ETA-treated organotypic cultures ( Figure 1D) was consistent with a previous observation of Dsg1 relocalization in canine PF. 65 Thus, we suggest that a common mechanism may underlie both toxin-and antibody-induced blistering. In pemphigus, IgG antibodies against desmogleins and desmocollins have been isolated from patients and the former are sufficient to induce pathology in mice or human epidermal explants.…”

Section: Discussionmentioning

confidence: 78%

Plakoglobin Rescues Adhesive Defects Induced by Ectodomain Truncation of the Desmosomal Cadherin Desmoglein 1

Simpson

Kojima

Cooper-Whitehair

et al. 2010

The American Journal of Pathology

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Desmoglein 1 (Dsg1) is a desmosomal cadherin that is essential to epidermal integrity. In the blistering diseases bullous impetigo and staphylococcal scaldedskin syndrome, pathogenesis depends on cleavage of Dsg1 by a bacterial protease, exfoliative toxin A, which removes residues 1 to 381 of the Dsg1 ectodomain. However, the cellular responses to Dsg1 cleavage that precipitate keratinocyte separation to induce blister formation are unknown. Here, we show that ectodomain-deleted Dsg1 (⌬381-Dsg1) mimics the toxin-cleaved cadherin, disrupts desmosomes, and reduces the mechanical integrity of keratinocyte sheets. In addition, we demonstrate that truncated Dsg1 remains associated with its catenin partner , plakoglobin , and causes a reduction in the levels of endogenous desmosomal cadherins in a dose-dependent manner , leading us to hypothesize that plakoglobin sequestration by truncated Dsg1 destabilizes other cadherins. Accordingly, a triple-point mutant of the ectodomain-deleted cadherin, which is uncoupled from plakoglobin, does not impair adhesion, indicating that this interaction is essential to the pathogenic potential of truncated Dsg1. Moreover, we demonstrate that increasing plakoglobin levels rescues cadherin expression, desmosome organization, and functional adhesion in cells expressing ⌬381-Dsg1 or treated with exfoliative toxin A. Finally, we report that histone deacetylase inhibition up-regulates desmosomal cadherins and prevents the loss of adhesion induced by Dsg1 truncation. These findings further our understanding of the mechanism of exfoliative toxin-induced pathology and suggest novel strategies to suppress blistering in bulbous impetigo and staphylococcal scalded-skin syndrome. Desmosomes are specialized intercellular adhesive organelles crucial for maintaining the integrity of tissues that endure mechanical stress, especially the epidermis. 1The adhesive interface of desmosomes is built from specialized cadherin family members, including four desmogleins (Dsg1-4) and three desmocollins (Dsc1-3), assembled at junctions between epidermal keratinocytes. Desmogleins and desmocollins cooperate to mediate adhesion with cadherins on neighboring cells via ectodo-

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“…These results indicate the suitability of the utilised antibodies on horse cryo-sectioned skin samples to define the distribution pattern of desmosomes and the usefulness of immunoblotting to investigate further the role of circulating antibodies in affected subjects. As suggested by Steeves et al (2002), the use of immunohistochemical staining for Dsg may be applied in the histopathological diagnosis to characterise skin histological changes occurring in PF.…”

Section: Discussionmentioning

confidence: 99%

“…The pathogenesis of PF has been intensively investigated in man and the molecular characteristics of human Dsgs analysed (Mahoney et al 1999). In the canine species Dsg-1 has been characterised and the hypothesis that this glycoprotein is the target antigen in PF is strongly supported (Suter et al 1993;Iwasaki et al 1997;Steeves et al 2002). However, contrasting evidence concerning a minor role of Dsg-1 in the pathogenesis of canine PF has been reported (Olivry et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Immunolocalisation of desmoglein-1 in equine muzzle skin

Miragliotta

Donadio

Felicioli

et al. 2010

Equine Veterinary Journal

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Desmogleins (Dsgs) are glycoproteins of the cadherin family that allow the formation of desmosomes via a Ca2+-dependent homophilic interaction. Desmosomes are cell-cell adhesion systems that contribute to the mechanical integrity of epidermis by linking to keratin intermediate filaments and, therefore, connecting the cytoskeleton of adjacent keratinocytes (Cozzani et al. 1994). On light microscopy, desmosomes appear as intercellular bridges. On electron microscopy they consist of symmetrical disc-like structures, which link the intermediate filaments system within cells to the plasma membrane and to adjacent cells (North et al. 1999). Four isoforms of Dsgs have been described in human (Whittock 2003), one in bovine (Koch et al. 1990; Puttagunta et al. 1994), 2 in canine (Muller et al. 2000; Aoki et al. 2002), 6 in murine (Whittock 2003) and, recently, one in porcine (Nishifuji et al. 2005) species. The production of autoantibodies against desmoglein-1 (Dsg-1) leads to the loss of epidermal cell-cell adhesion responsible for pustular lesions in the life-threatening skin disease pemphigus foliaceus (PF) (McMillan and Shimizu 2001). The pathogenesis of PF has been intensively investigated in man and the molecular characteristics of human Dsgs analysed (Mahoney et al. 1999). In the canine species Dsg-1 has been characterised and the hypothesis that this glycoprotein is the target antigen in PF is strongly supported (Suter et al. 1993; Iwasaki et al. 1997; Steeves et al. 2002). However, contrasting evidence concerning a minor role of Dsg-1 in the pathogenesis of canine PF has been reported (Olivry et al. 2006). The first case of equine PF was reported by Barnick and Gutzeit (1891) and since 1980 only a few such reports have been documented in this species (Peter et al. 1981; Messer and Knight 1982; Rothwell et al. 1985; Laing et al. 1992; Wohlsein et al. 1994; Stahli et al. 2005). Recently, Vandenabeele et al. (2004) and Zabel et al. (2005) reviewed equine PF. In horses diagnosis is based mainly on clinical and histopathological features, which strictly resemble those described in other species and on the response to immunosuppressive drugs (Vandenabeele et al. 2004; Zabel et al., 2005). Nevertheless, the presence of Dsg-1 in equine epidermis has never been documented and whether this transmembrane protein is targeted by circulating antibodies in horses with PF is still unknown. This study documents the presence of a pericellular antigen in horse muzzle skin by immunohistochemistry using 2 commercially available monoclonal antibodies raised against bovine Dsg-1-2 and human Dsg-1 and the presence of 2 bands by immunoblotting analyses using anti-human-Dsg-1

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Altered Immunohistochemical Staining for Desmoglein in Skin Biopsies in Canine Pemphigus Foliaceus

Cited by 10 publications

References 9 publications

Metaflumizone–amitraz (Promeris)‐associated pustular acantholytic dermatitis in 22 dogs: evidence suggests contact drug‐triggered pemphigus foliaceus

Metaflumizone–amitraz (Promeris)‐associated pustular acantholytic dermatitis in 22 dogs: evidence suggests contact drug‐triggered pemphigus foliaceus

Plakoglobin Rescues Adhesive Defects Induced by Ectodomain Truncation of the Desmosomal Cadherin Desmoglein 1

Immunolocalisation of desmoglein-1 in equine muzzle skin

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