Endocytosis of IgG, Desmoglein 1, and Plakoglobin in Pemphigus Foliaceus Patient Skin

Pemphigus foliaceus (PF) is one of the two main forms of pemphigus and is characterized by circulating IgG to the desmosomal cadherin desmoglein 1 (DSG1) and by subcorneal blistering of the skin. The pathomechanism of blister formation in PF is unknown. Previously we have shown that PF IgG induces aggregation of DSG1, plakoglobin (PG), and IgG outside of desmosomes, what in immunofluorescence of PF patient skin visualizes as a granular IgG deposition pattern with a limited number of coarse IgG aggregates between cells. Here we have investigated the fate of these aggregates in skin and found that these are cleared by endocytosis. We performed double immunofluorescence staining on snap-frozen skin biopsies of six PF patients for the following molecules: IgG, the desmosomal proteins DSG1 and DSG3, desmocollins 1 and 3, PG, desmoplakin and plakophilin 3, and for the endosomal marker early endosomal antigen 1 and the lysosomal markers cathepsin D and lysosomal-associated membrane protein 1. Endosomes were present in all cells but did not make contact with the aggregates in the basal and suprabasal layers. In the higher layers they moored to the aggregates, often symmetrically from two adjacent cells, and IgG, DSG1, and PG were taken up. Finally these endosomes became localized perinuclear. Endocytosis was only observed in perilesional or lesional skin but not in non-lesional skin. Older immunoelectron microscopic studies have suggested that in PF skin endocytosis of detached desmo...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Authors: Popescu IA, Statescu L, Vata D, Porumb-Andrese E, Patrascu AI, Grajdeanu IA, Solovastru LG Abstract The place of pemphigus vulgaris (PV) among autoimmune bullous dermatoses is well known. In pemphigus, IgG autoantibodies are directed against desmogleins 1 and 3, which are part of the cadherin family of cell-cell adhesion molecules. These structures are responsible for maintaining the intercellular adherence in stratified squamous epithelia, such as the skin and oral mucosa. The incidence of autoimmune bullous dermatoses is steadily increasing, being associated with a high degree of morbidity. The pathophys...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
AbstractPemphigus vulgaris (PV) is a rare autoimmune blistering disease involving the skin and mucous membranes. The prevalence of esophageal involvement remains uncertain. The aim of our study was to determine the frequency of esophageal involvement in patients with PV. This is a single-center electronic database retrospective review of patients with a diagnosis of PV. Data abstracted included demographics, disease characteristics (biopsy results, symptoms, areas affected, treatments), and esophagogastroduodenoscopy (EGD) reports. Of the 111 patients that met eligibility criteria, only 22 (19.8%) underwent EGD. Demographi...
Source: Dysphagia - Category: Speech-Language Pathology Source Type: research
Publication date: 7–13 September 2019Source: The Lancet, Volume 394, Issue 10201Author(s): Enno Schmidt, Michael Kasperkiewicz, Pascal JolySummaryPemphigus consists of a group of rare and severe autoimmune blistering diseases mediated by pathogenic autoantibodies mainly directed against two desmosomal adhesion proteins, desmoglein (Dsg)1 and Dsg3 (also known as DG1 and DG3), which are present in the skin and surface-close mucosae. The binding of autoantibodies to Dsg proteins induces a separation of neighbouring keratinocytes, in a process known as acantholysis. The two main pemphigus variants are pemphigus vulgaris,...
Source: The Lancet - Category: General Medicine Source Type: research
Hailey-Hailey disease (HHD), or familial benign pemphigus, is a heritable skin condition characterized by chronic waxing and waning blisters in intertriginous areas. The disease is caused by a mutation of the ATP2C1 gene, encoding a Ca+2-ATPase. Many treatments have been used for the disease, yet there is no effective treatment due to the lack of gene therapy. There are several reports of the use of low-dose naltrexone (LDN) to treat HHD. We add 3 cases of biopsy-proven HHD treated with naltrexone to the current literature.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
Autoimmune bullous dermatoses (AIBD) are characterized by circulating autoantibodies that are either directed against epidermal antigens or deposited as immune complexes in the basement membrane zone. The complement system (CS) can be activated by autoantibodies, thereby triggering activation of specific complement pathways. Local complement activation induces a pathogenic inflammatory response that eventually results in the formation of a sub- or intraepidermal blister. Deposition of complement components is routinely used as a diagnostic marker for AIBD. Knowledge from different animal models mimicking AIBD and depositio...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Paraneoplastic autoimmune multi-organ syndrome (PAMS) is a rare clinical condition characterized by variable and heterogeneous clinical phenotypes in the presence of neoplasias which largely depend on the activation of humoral and cellular immune responses. Clinically, these patients present with a spectrum of pemphigus-like lesions to graft-vs-host-disease-like exanthemas with a lichenoid inflammatory infiltrate in the skin. PAMS is occasionally associated with thymoma. We here present a patient with relapsing thymoma who developed PAMS with several cutaneous and extracutaneous autoimmune disorders. Peripheral blood lym...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Authors: Kiritsi D, Schauer F Abstract Autoimmune blistering skin disorders represent a rare group of autoantibody-induced dermatoses against desmosomal and hemidesmosomal molecules. The common age of onset for pemphigus and pemphigoid, as well as dermatitis herpetiformis, encompasses the adult age, but all these disorders can be observed neonatally and/or during childhood. If the disease occurs postpartum or neonatally, physicians should consider transplacental transmission of pathogenic maternal immunoglobulin G (IgG)-autoantibodies, and both mother and child should be included in the diagnostic work up. If ...
Source: Der Hautarzt: Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete - Category: Dermatology Tags: Hautarzt Source Type: research
A 45-year-old man suffering from dermal blistering disease with proteinuria and hematuria underwent renal biopsy. The renal biopsy specimen suggested proliferative glomerulonephritis with monoclonal IgG deposits under routine light, immunofluorescence and electron microscopy. The staining for IgG subclasses (IgG1 and IgG2) and κ/λ light chain indicated secondary immune complex type MPGN type 3. The patient had been diagnosed as having dermatitis herpetiformis (DH), a phenotype of gluten hypersensitivity prior to the appearance of the renal abnormality. Although common autoantibodies might be related to the pat...
Source: Case Reports in Nephrology and Dialysis - Category: Urology & Nephrology Source Type: research
We present the clinical case of the patient, followed for a total of 86  weeks, with ten relapses secondary to probable cocaine use. The patient was admitted to the emergency department after presenting polymorphic dermatosis characterized by blisters, vesicles, and excoriations extending from the oral cavity to the thorax, and to the inguinal and genital regions, aff ecting approximately 35 % of the body surface area with a score of 56 on the Pemphigus Skin Disorder Index. Skin biopsies were compatible with PV diagnosis. The patient had clinical improvement with a combination of methylprednisolone 500 ...
Source: Dermatology and Therapy - Category: Dermatology Source Type: research
ConclusionIntractable mucocutaneous lesions with a concurrent tumor in children strongly indicate PNP resulting from CD. Because stomatitis or skin erosion may be the first presentation, mucocutaneous tissue biopsy and early detection of the underlying tumor are important. Earlier diagnosis is mandatory for the effective treatment of PNP and pulmonary involvement.
Source: APLAR Journal of Rheumatology - Category: Rheumatology Authors: Tags: ORIGINAL ARTICLE Source Type: research
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