Diagnosing Skin Disease
Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang in Roxburgh's Common Skin Diseases, 2022
A variety of causes are associated with blistering dermatosis, including autoimmune, infectious, and inflammatory etiologies. Autoantibodies against desmogleins 1 and 3, which are components of desmosomes that keep keratinocytes attached to one another, resulting in acantholysis, or a loss in intercellular connections, and can lead to intraepidermal blisters. In contrast, autoantibodies against components of hemidesmosomes of the dermo-epidermal junction in bullous pemphigoid result in subepidermal blisters (Figure 2.6). Herpesvirus infection of the epidermis may result in acantholysis and varying degrees of epidermal necrosis, which can lead to intraepidermal or subepidermal blisters. Significant intercellular edema in allergic contact or nummular dermatitis results in intraepidermal blisters. Any process that weakens the dermo-epidermal junction may result in a subepidermal blister (Figure 2.7). Severe dermal edema from a variety of sources may also result in a subepidermal blister (e.g., lymphedema blister, bullous insect bite, and bullous Sweet syndrome). Depending on the severity and acuity, most interface dermatitides, which are associated with a variable degree of necrosis of keratinocytes at the dermo-epidermal junction, have a subepidermal bullous expression. Examples include bullous erythema multiforme, bullous lichen planus, and bullous fixed-drug eruption.
Dermatologic diseases and pregnancy
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
The pemphigoid gestationis antigen has been characterized as a 180-kDa glycoprotein found in the lamina lucida of the basement membrane of skin and placenta (42,43). It is an interesting observation that pemphigoid gestationis antigen may first appear in the placenta during the second trimester of pregnancy, coinciding with the time course of the development of pemphigoid gestationis (44). This 180-kDa antigen is also known as bullous pemphigoid antigen 2 and most recently as type XVII collagen. This is a transcellular glycoprotein in the hemidesmosome with both a cytoplasmic and extracellular domain. The function of the hemidesmosome is to anchor the basal cells of the epidermis to the basement membrane thus keeping it attached to the dermis. The NC16A segment of the 180-kDa antigen is the immunoreactive site in the majority of affected patients (38).
Comparative Anatomy, Physiology, and Biochemistry of Mammalian Skin
David W. Hobson in Dermal and Ocular Toxicology, 2020
The basal cell membrane of the epidermal-dermal junction is not always smooth. It may be irregular, forming finger-like projections into the dermis. The cell membrane consists of three layers, a thick internal leaflet, an electron lucent layer, and a thin external leaflet. Hemidesmosomes are sometimes found along the internal leaflet of the cell membrane. Occasionally, small vesicles (pinocytotic) are seen near and on the plasma membrane. The lamina lucida portion of the basement membrane is electron-lucent except in the hemidesmosome area, where one can see a sub-basal dense plaque and some fine filaments. The next layer is the basal lamina which is electron dense and may contain fibrillar components in an amorphous substance. The basal lamina is thicker and denser in regions beneath hemidesmosomes.
Suspended cell lines for inactivated virus vaccine production
Published in Expert Review of Vaccines, 2023
Jiayou Zhang, Zhenyu Qiu, Siya Wang, Zhenbin Liu, Ziling Qiao, Jiamin Wang, Kai Duan, Xuanxuan Nian, Zhongren Ma, Xiaoming Yang
Integrins are heterodimers composed of an α subunit noncovalently associated with a β subunit with 18 α subunits and 9 β subunits currently identified. The β1-containing integrin (Itgb1) mainly mediates adhesion between cells and ECM components. It has been experimentally demonstrated that Itgb1 knockdown reduces iPSC-ECM adhesion and simultaneously increases ECM cross-migration in vitro [91]. Additionally, it plays a role in reducing cell adhesion between epidermal cells and ECM and keratinocytes [92,93]. Hemidesmosomes (HDs), with α6β4-integrin as the core, act as complex adhesive junctions linking the basement membrane to the intracellular keratin cytoskeleton and mediate stable anchoring to the ECM. α6β4 is a receptor for laminin, which mainly binds to laminin 5. Thus, disruption of HDs by depleting α6- or β4-integrin expression promotes collective cell migration and modulates migration activity. Experiments have shown that the destruction of HDs can affect the molecular diffusion rate of focal adhesion kinase (FAK), thereby reducing the adhesion of cell adhesins [94]. Additionally, some experiments have demonstrated that its deletion will reduce proliferation, survival, and differentiation of keratinocytes [95].
Targeting interleukin 4 and interleukin 13: a novel therapeutic approach in bullous pemphigoid
Published in Annals of Medicine, 2023
Fangyuan Chen, Yiman Wang, Xinyi Chen, Nan Yang, Li Li
Bullous pemphigoid (BP) is an autoimmune bullous skin disease mediated by pathogenic autoantibodies that target the hemidesmosome proteins BP antigen 180 (BP180) and BP antigen 230 (BP230) [1–3]. Clinically, BP is characterized by large, tense blisters and erythema, and it mostly affects senior adults [4]. Histologically, BP presents with subepidermal blisters with neutrophil and eosinophil infiltration. BP180 is a transmembrane glycoprotein with a globular cytoplasmic N-terminal domain, whereas BP230 is an intracellular constituent of hemidesmosome plaques [1,2]. Most patients with BP have circulating immunoglobulin (Ig) G autoantibodies that target BP180, particularly in non-collagenous domain 16A (NC16A), which is the immunodominant region recognized by autoreactive T and B cells [5]. In BP, T cell responds with both T helper 1 (Th1) and T helper 2 (Th2) cells. Thus, in patient serum, both Th2-mediated IgG4 and Th1-mediated IgG1 autoantibodies are present [6]. However, the presence of IgG autoantibodies does not explain all of the clinical features involved in BP. Factors other than IgG autoantibodies may also contribute to the pathogenesis of cutaneous inflammation in BP, such as T-helper autoreactive lymphocytes, cytokines, IgE, and eosinophils [7,8]. Whereas interleukin-4 (IL-4) and interleukin-13 (IL-13) are two key cytokines in Th2 autoimmune response, IL-4 and IL-13 are presumed to contribute to the pathogenesis of BP.
Granzyme B as a therapeutic target: an update in 2022
Published in Expert Opinion on Therapeutic Targets, 2022
Alexandre Aubert, Michael Lane, Karen Jung, David J. Granville
Pemphigoid diseases (PD) are a group of seven autoimmune disorders characterized by subepithelial blistering in response to autoantibody production against structural components of the dermal-epidermal junction (DEJ) [57]. The DEJ is a multiprotein complex that comprises architectural hemidesmosomal proteins of the BM (Laminins and ColIV), ColVII anchoring fibrils, as well as cell surface receptors (ColXVII and α6β4 integrins). Altogether, hemidesmosomes attach the intracellular cytoskeleton of basal keratinocytes to the lamina lucida and lamina densa of the BM, thus delineating the stratum basale of the epidermis and maintaining homeostasis. Hemidesmosomes also contribute to skin integrity by linking the epidermis/BM complex to the underlying dermal connective tissue (Figure 2, left panel) [58,59].