Autoantibodies against desmocollins in European patients with pemphigus

Müller, Ralf; Heber, B.; Hashimoto, Takashi; Messer, Gerald; Müllegger, Robert R.; Niedermeier, A.; Hertl, Michael

doi:10.1111/j.1365-2230.2009.03241.x

Cited by 67 publications

(77 citation statements)

References 21 publications

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“…4,5 Because the results of reactivity with Dsc1, Dsc2, and Dsc3 in this study were almost identical between cDNA transfection method and novel Dsc ELISAs, combination of these tests should be a reliable method to detect autoantibodies to Dscs in various types of pemphigus in the future. In case 2, immunoblotting of normal human epidermal cell extracts showed the 190-kDa periplakin-like and 230-kDa BP230-like bands.…”

Section: Discussionmentioning

confidence: 90%

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Two Cases of Pemphigus Vegetans With IgG Anti–Desmocollin 3 Antibodies

et al. 2013

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Section: Discussionmentioning

confidence: 90%

“…[4][5][6][7][8][9] However, precise prevalence of IgG anti-Dsc autoantibodies in various types of pemphigus, including pemphigus vegetans, has not been fully elucidated. To answer this question, extensive studies using Dsc ELISAs in large numbers of patients with pemphigus should be performed.…”

Section: Discussionmentioning

confidence: 99%

Two Cases of Pemphigus Vegetans With IgG Anti–Desmocollin 3 Antibodies

et al. 2013

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“…We present a case of anti-Dsc3 PV, illustrated in a patient with typical mucosal disease. Previously, atypical or paraneoplastic pemphigus patients with human Dsc3 immunoreactivity have been described, 17,[22][23][24] although autoantibodies in these patients reacted with multiple skin antigens, and pathogenicity against Dsc3 was not demonstrated, raising the possibility that the Dsc3 autoantibodies may not have caused disease, but instead arose secondarily as a result of epidermal damage. Figure 2A and unpublished data in- bearing an E tag were produced in a baculovirus expression system.…”

Section: Discussionmentioning

confidence: 99%

Autoimmunity to Desmocollin 3 in Pemphigus Vulgaris

Mao

Nagler

Farber

et al. 2010

The American Journal of Pathology

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Pemphigus vulgaris is a blistering disease associated with autoantibodies to the desmosomal adhesion protein, desmoglein 3. Genetic deficiency of desmoglein 3 in mice mimics autoimmunity to desmoglein 3 in pemphigus vulgaris, with mucosal-dominant blistering in the suprabasal layer of the epidermis. Mice with an epidermal-specific deletion of desmocollin 3, the other major desmosomal cadherin isoform expressed in the basal epidermis, develop suprabasal blisters in skin that are histologically identical to those observed in pemphigus vulgaris, suggesting that desmocollin 3 might be a target of autoantibodies in some pemphigus vulgaris patients. We now demonstrate that desmocollin 3 is an autoantigen in pemphigus vulgaris, illustrated in a patient with mucosaldominant blistering. Six of 38 pemphigus vulgaris and one of 85 normal serum samples immunoprecipitate desmocollin 3 (P ‫؍‬ 0.003). Incubation of patient IgG with human keratinocytes causes loss of intercellular adhesion, and adsorption with recombinant desmocollin 3 specifically prevents this pathogenic effect. Additionally, anti-desmocollin 3 sera cause loss of keratinocyte cell surface desmocollin 3, but not desmoglein 3 by immunofluorescence , indicating distinct cellular pathogenic effects in anti-desmocollin and antidesmoglein pemphigus , despite their identical clinical presentations. These data demonstrate that desmocollin 3 is a pathogenic autoantigen in pemphigus vulgaris and suggest that pemphigus vulgaris is a histological reaction pattern that may result from autoimmunity to desmoglein 3, desmocol-

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“…PF-IgG contained Dsg1 but no Dsg3 Abs. For detection of possible Dsc3 Abs in pemphigus IgG fractions, we applied enzyme-linked immunosorbent assay measurements and immunoblotting analysis as described elsewhere in detail (16). All three sera were negative for Dsc3 by enzyme-linked immunosorbent assay (Table 1) and in Western blots (data not shown).…”

Section: Methodsmentioning

confidence: 99%

Desmocollin 3-mediated Binding Is Crucial for Keratinocyte Cohesion and Is Impaired in Pemphigus

Spindler

Heupel

Efthymiadis

et al. 2009

Journal of Biological Chemistry

104

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Desmocollin (Dsc) 1-3 and desmoglein (Dsg) 1-4, transmembrane proteins of the cadherin family, form the adhesive core of desmosomes. Here we provide evidence that Dsc3 homo-and heterophilic trans-interaction is crucial for epidermal integrity. Single molecule atomic force microscopy (AFM) revealed homophilic trans-interaction of Dsc3. Dsc3 displayed heterophilic interaction with Dsg1 but not with Dsg3. A monoclonal antibody targeted against the extracellular domain reduced homophilic and heterophilic binding as measured by AFM, caused intraepidermal blistering in a model of human skin, and a loss of intercellular adhesion in cultured keratinocytes. Because autoantibodies against Dsg1 are associated with skin blistering in pemphigus, we characterized the role of Dsc3 binding for pemphigus pathogenesis. In contrast to AFM experiments, laser tweezer trapping revealed that pemphigus autoantibodies reduced binding of Dsc3-coated beads to the keratinocyte cell surface. These data indicate that loss of heterophilic Dsc3/Dsg1 binding may contribute to pemphigus skin blistering.

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Autoantibodies against desmocollins in European patients with pemphigus

Abstract: These findings support the concept that desmocollins are not important autoantigens in PV.

Cited by 67 publications

References 21 publications

Two Cases of Pemphigus Vegetans With IgG Anti–Desmocollin 3 Antibodies

Two Cases of Pemphigus Vegetans With IgG Anti–Desmocollin 3 Antibodies

Autoimmunity to Desmocollin 3 in Pemphigus Vulgaris

Desmocollin 3-mediated Binding Is Crucial for Keratinocyte Cohesion and Is Impaired in Pemphigus

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