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Concept: Epidermolysis bullosa acquisita

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Type VII collagen (Col7) is the major component of anchoring fibrils and very important for skin integrity. This is emphasized by the Col7 related skin blistering diseases dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita. Structural data that provides insights into the interaction network of Col7 and thus providing a basis for a better understanding of the pathogenesis of the diseases is missing. We proved that the von-Willebrand-factor A like domain 2 (vWFA2) of Col7 is responsible for type I collagen binding. The interaction has a K(D) value of 90 μM as determined by SPR and is enthalpy driven as derived from the van’t Hoff equation. Furthermore, a hitherto unknown interaction of this domain with type IV collagen was identified. The interaction of vWFA2 with type I collagen is sensitive to the presence of magnesium ions, however, vWFA2 does not contain a magnesium binding site thus magnesium must bind to type I collagen. A lysine residue has been identified to be crucial for type I collagen binding. This allowed localization of the binding site. Mutational analysis suggests different interaction mechanisms in different species and that these interactions might be of covalent nature.

Concepts: Protein, Collagen, Atom, Epidermolysis bullosa, Structural proteins, Epidermolysis bullosa acquisita, Epidermolysis bullosa dystrophica, Van 't Hoff equation

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A 50-year-old man presented with tense noninflammatory bullae and erosions on trauma-prone areas of skin and the mucosae. There was also atrophic scarring, milia formation, onychodystrophy, and anonychia.

Concepts: Collagen, Skin, Epidermolysis bullosa, Epidermolysis bullosa acquisita

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Epidermolysis bullosa acquisita (EBA) and anti-p200 pemphigoid are uncommon subepidermal autoimmune bullous diseases caused by autoantibodies against the 200-kDa protein and 290-kDa type VII collagen, respectively. Here we describe a patient with autoantibodies against both 200-kDa and 290-kDa antigens.A 63-year-old-man had itchy tense blisters and edematous erythemas scattered on his trunk, buttocks, extremities and soles (Fig. 1a). There were no ocular or mucosal lesions. Psoriatic skin lesions were not observed. There was no personal or family history of serious diseases. This article is protected by copyright. All rights reserved.

Concepts: Immune system, Protein, Collagen, All rights reserved, Copyright, Epidermolysis bullosa, Epidermolysis bullosa acquisita, Epidermolysis bullosa dystrophica

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Type VII collagen (COL7), a major component of anchoring fibrils in the epidermal basement membrane zone, has been characterized as a defective protein in dystrophic epidermolysis bullosa and as an autoantigen in epidermolysis bullosa acquisita. Although COL7 is produced and secreted by both epidermal keratinocytes and dermal fibroblasts, the role of COL7 with regard to the epidermis is rarely discussed. This review focuses on COL7 physiology and pathology as it pertains to epidermal keratinocytes. We summarize the current knowledge of COL7 production and trafficking, its involvement in keratinocyte dynamics, and epidermal carcinogenesis in COL7 deficiency and propose possible solutions to unsolved issues in this field.

Concepts: Collagen, Fibroblast, Epidermis, Skin anatomy, Keratinocyte, Epidermolysis bullosa, Epidermolysis bullosa acquisita, Epidermolysis bullosa dystrophica

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It has been postulated that periodic acid-Schiff staining of basement membrane can predict direct immunofluorescence patterns seen in epidermolysis bullosa acquisita and bullous pemphigoid. It has also been suggested that the type of inflammatory infiltrate or presence of fraying of basal keratinocytes may differentiate these two conditions.

Concepts: Histology, Epidermolysis bullosa, Epidermolysis bullosa acquisita

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Dear editor, we read with great interest the article ‘Human orf complicated by epidermolysis bullosa acquisita’ by Zeulgaray and colleagues.1 Recently, a Moroccan patient who contracted orf (fig. 1a) after slaughtering a sheep during Eid Al-Adha was admitted to our hospital and developed a similar pruritic vesiculobullous eruption predominantly on the hands and forearms (fig. 1b). Hematoxylin and eosin staining of punch biopsies from areas of the vesicullobullous eruption showed spongiotic dermatitis with eosinophilia, most consistent with an id reaction. This article is protected by copyright. All rights reserved.

Concepts: All rights reserved, Copyright, Epidermolysis bullosa, Epidermolysis bullosa acquisita

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Circulating anti-type VII collagen autoantibodies are frequently detected in patients with recessive dystrophic epidermolysis bullosa (RDEB). However, evidence supporting their pathogenic role in inducing epidermolysis bullosa acquisita (EBA) has been provided for only 1 individual with dominant dystrophic epidermolysis bullosa (DDEB). We describe here a patient who presented with dystrophic toenails since early childhood and developed trauma-induced skin blisters and oral erosions at age 26 years. Direct immunofluorescence showed IgG deposits with a u-serrated pattern along the cutaneous basement membrane zone, while no change in the expression of collagen VII could be detected by antigen mapping. High-titre anti-collagen VII antibodies were detected by enzyme-linked immunoassay (ELISA). In parallel, sequencing of epidermolysis bullosa (EB) genes identified compound heterozygous COL7A1 missense c.410G>A (p.Arg137Gln) and splicing c.3674C>T (p.Ala1225_Gln1241del) mutations, previously unrecognized in dystrophic epidermolysis bullosa (DEB). Thus, our patient had RDEB “nails-only” and developed mechanobullous EBA in adulthood. These data support a pathogenic role of circulating autoantibodies to collagen VII in inducing EBA in selected patients with DEB. Unforeseen worsening of skin symptoms in DEB should prompt laboratory investigations for EBA.

Concepts: Immune system, Antibody, Protein, Collagen, Keratin, Epidermolysis bullosa, Epidermolysis bullosa acquisita, Epidermolysis bullosa dystrophica

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Epidermolysis bullosa acquisita (EBA) is a complex autoimmune bullous disease disease with variable clinical presentations and multiple possible diagnostic tests making an international consensus on diagnosis of EBA needed.

Concepts: Death, Medical terms, Diagnosis, Epidermolysis bullosa, Epidermolysis bullosa acquisita

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Pemphigus and pemphigoid diseases are organ-specific autoimmune blistering diseases (AIBD), characterized and caused by autoantibodies to structural components of the skin (1). The autoantigens targeted in pemphigus are desmoglein 1 and 3, two proteins of the desmosomal structure, while the autoantigens in pemphigoid diseases (PD) are components of the basal membrane. For example, bullous pemphigoid (BP), the most frequent PD is characterized by autoantibodies against type XVII collagen (COL17, BP180) and BP230, and epidermolysis bullosa acquisita (EBA) is caused by autoantibodies against type VII collagen (COL7). This article is protected by copyright. All rights reserved.

Concepts: Immune system, Collagen, Autoimmune diseases, All rights reserved, Copyright, Epidermolysis bullosa, Epidermolysis bullosa acquisita, Epidermolysis bullosa dystrophica

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Direct immunofluorescence microscopy (DIF) of a skin biopsy specimen is the reference standard for the diagnosis of pemphigoid diseases (PD). Serration pattern analysis enables differentiation of epidermolysis bullosa acquisita (EBA) from other PD using DIF microscopy alone. However, practice gaps need to be addressed for implication of this technique in daily routine diagnostics.

Concepts: Medical terms, Biopsy, Diagnosis, Greek loanwords, Immunofluorescence, Epidermolysis bullosa, Epidermolysis bullosa acquisita