scholarly journals A Hypothesis Concerning a Potential Involvement of Ceramide in Apoptosis and Acantholysis Induced by Pemphigus Autoantibodies

2010 ◽  
Vol 2010 ◽  
pp. 1-8
Author(s):  
Wendy B. Bollag
Keyword(s):  
Autoimmune Diseases ◽  
Ultraviolet Irradiation ◽  
Cell Adhesion Molecule ◽  
Sun Exposure ◽  
Pemphigus Vulgaris ◽  
Skin Lesions ◽  
Epidermal Keratinocytes ◽  
Pemphigus Foliaceus ◽  
Endemic Pemphigus Foliaceus ◽  
A Cell

Autoimmune diseases affect more than 50 million Americans, resulting in significant healthcare costs. Most autoimmune diseases occur sporadically; however, endemic pemphigus foliaceus (EPF) is an autoimmune skin disease localized to specific geographic loci. EPF, and the related diseases pemphigus vulgaris (PV) and pemphigus foliaceus (PF), are characterized by skin lesions and autoantibodies to molecules found on epidermal keratinocytes. A variant of EPF in patients from El Bagre, Colombia, South America, has recently been reported to be distinct from previously described loci in Brazil and Tunisia epidemiologically and immunologically. As in PF and EPF, El Bagre EPF patients exhibit autoantibodies towards desmoglein-1, a cell adhesion molecule critical for maintaining epidermal integrity. An association of El Bagre EPF with sun exposure has been detected, and ultraviolet irradiation also exacerbates symptoms in PV, PF and EPF. Our hypothesis is that: (1) the autoantibodies generate pathology through an alteration in ceramide metabolism in targeted keratinocytes, resulting in apoptosis and/or cell death and acantholysis, but only when the cell's ability to metabolize ceramide is exceeded, and (2) apoptosis in response to this altered ceramide metabolism is initiated and/or exacerbated by other agents that increase ceramide levels, such as cytokines, ultraviolet irradiation, and senescence.

UVB-induced acantholysis in endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris

2000 ◽  
Vol 42 (4) ◽  
pp. 571-576 ◽  
Author(s):  
Vitor M.S. Reis ◽  
Roseli P. Toledo ◽  
Argelia Lopez ◽  
Luis A. Diaz ◽  
Jose E.C. Martins
Keyword(s):  
Pemphigus Vulgaris ◽  
Pemphigus Foliaceus ◽  
Endemic Pemphigus Foliaceus

Apoptosis is not required for acantholysis in pemphigus vulgaris

2009 ◽  
Vol 296 (1) ◽  
pp. C162-C172 ◽  
Author(s):  
Enno Schmidt ◽  
Judith Gutberlet ◽  
Daniela Siegmund ◽  
Daniela Berg ◽  
Harald Wajant ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Pemphigus Vulgaris ◽  
Human Keratinocytes ◽  
Skin Lesions ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Epidermal Keratinocytes ◽  
Death Domain ◽  
Human Epidermal Keratinocytes ◽  
Desmosomal Cadherins ◽  
Normal Human

The autoimmune blistering skin disease pemphigus vulgaris (PV) is caused primarily by autoantibodies against desmosomal cadherins. It was reported that apoptosis can be detected in pemphigus skin lesions and that apoptosis can be induced by PV-IgG in cultured keratinocytes. However, the role of apoptosis in PV pathogenesis is unclear at present. In this study, we provide evidence that apoptosis is not required for acantholysis in PV. In skin lesions from two PV patients, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positivity, but not cleaved caspase-3, was detected in single keratinocytes in some lesions but was completely absent in other lesions from the same patients. In cultures of human keratinocytes (HaCaT and normal human epidermal keratinocytes), PV-IgG from three different PV patients caused acantholysis, fragmented staining of Dsg 3 staining, and cytokeratin retraction in the absence of nuclear fragmentation, TUNEL positivity, and caspase-3 cleavage and hence in the absence of detectable apoptosis. To further rule out the contribution of apoptotic mechanisms, we used two different approaches that are effective to block apoptosis induced by various stimuli. Inhibition of caspases by z-VAD-fmk as well as overexpression of Fas-associated death domain-like interleukin-1β-converting enzyme (FLICE)-like inhibitory proteins FLIPL and FLIPS to inhibit receptor-mediated apoptosis did not block PV-IgG-induced effects, indicating that apoptosis was not required. Taken together, we conclude that apoptosis is not a prerequisite for skin blistering in PV but may occur secondary to acantholysis.

scholarly journals Endemic pemphigus in the peruvian Amazon: epidemiology and risk factors for the development of complications during treatment

2012 ◽  
Vol 87 (6) ◽  
pp. 838-845 ◽  
Author(s):  
Willy Ramos ◽  
Gina Rocio Chacon ◽  
Carlos Galarza ◽  
Ericson Leonardo Gutierrez ◽  
Maria Eugenia Smith ◽  
...  
Keyword(s):  
Risk Factors ◽  
Binary Logistic Regression ◽  
Pemphigus Vulgaris ◽  
Pemphigus Foliaceus ◽  
Peruvian Amazon ◽  
Clinical Form ◽  
Autoimmune Blistering Disease ◽  
Clinical Variant ◽  
Endemic Pemphigus Foliaceus ◽  
Epidemiologic Characteristics

BACKGROUND: Pemphigus is an autoimmune blistering disease. According to a report, in areas of endemic pemphigus foliaceus (EPF) in Peru there are cases of pemphigus vulgaris with epidemiologic, clinical and histopathologic characteristics similar to those of "endemic pemphigus vulgaris" (EPV) in Brazil. OBJECTIVES: To determine the clinical and epidemiologic characteristics of endemic pemphigus and the risk factors of patients for developing complications during treatment. METHODS: A study was carried out from July 2003 to March 2008. The study population was 60 patients with EPF and 7 patients with EPV evaluated in hospitals and clinics in the Peruvian Amazon and Lima. A multivariate analysis was carried out using binary logistic regression. RESULTS: The average age of EPF patients was 31.4 years; 55% were men; 60% presented the generalized clinical variant. Non-compliance with the treatment was seen in 57.1% of the patients. Thirty-five percent presented complications (e.g. pyodermitis and pyelonephritis) during treatment. The risk factors for developing complications during treatment were non-compliance with the treatment and having the generalized clinical form. In the EPV group, the average age was 21.7 years; 71.4% were men. All patients presented with the mucocutaneous clinical variant and the initial presentation consisted of oral mucosa lesions; 71.4% presented complications during treatment, pyodermitis being the most frequent. CONCLUSIONS: Non-compliance with the treatment and the generalized clinical form are risk factors for the development of complications during treatment of patients with EPF. Peru indeed has EPV cases with epidemiologic characteristics similar to EPF. Living in a rural area may represent a risk factor for the development of complications during treatment of patients with EPV.

scholarly journals Epidemiological and clinical characteristics of patients with pemphigus treated in Białystok in 2001-2018

2020 ◽  
pp. 457-465
Keyword(s):  
Rural Areas ◽  
Clinical Characteristics ◽  
Pemphigus Vulgaris ◽  
Skin Lesions ◽  
Immunosuppressive Agent ◽  
Pemphigus Foliaceus ◽  
Aim Analysis ◽  
North East ◽  
Oropharyngeal Cavity ◽  
Medical University

BACKGROUND. Pemphigus is a group of potentially fatal dermatological autoimmune disorders. AIM. Analysis of cases of pemphigus vulgaris (PV) and pemphigus foliaceus (PF) newly diagnosed and treated at the Department of Dermatology and Venereology, Medical University of Białystok, North-east Poland in years 2001-2018. MATERIAL AND METHODS. A retrospective analysis and comparison of sociodemographic, epidemiological and clinical characteristics of PV and PF patients, including: age, gender, residency, initial severity of skin lesions, involvement of mucous membranes, co-morbidities and their treatment, efficacy of therapy. RESULTS. Sixty-two new cases – 41 (66.13%) of PV and 21 (33.87%) of PF were diagnosed. The average age of PV patients was 54.85±12.35 years and those of PF – 63.81±31.52 years, P<0.05. Females constituted 75.61% and 61.90% in PV and PF group, respectively. Majority of patients with PV were residents of urban and these with PF – of rural areas (70.73% and 66.67%, respectively). On admission, 14 patients with PV (34.15%) and 11 with PF (52.38%) had more than 30% of body surface area involved. In 22 (53.66%) PV mucous membrane (oropharyngeal cavity) was involved. Ten (24.39%) patients with PV and 12 (57.14%) - with PF had more than one concomitant disorder (P<0.05). In treatment prednisone in monotherapy or with additional immunosuppressive agent was mainly used. The disease relapsed within three years after achieving clinical and immunological remission in 29.27% of PV and in 38.10% of PF patients. CONCLUSIONS. PF patients are older than PV ones, more frequently live in rural areas, have more comorbidities. Females constitute majority of pemphigus patients. The disease may relapse in about one third of patients. Because of frequent comorbidities, also these related to pemphigus treatment, patients with pemphigus require complex and multispecialistic medical care.

Anti-Desmoglein 1 and 3 Autoantibody Levels in Endemic Pemphigus Foliaceus and Pemphigus Vulgaris from Brazil

2016 ◽  
Vol 62 (07/2016) ◽  
Author(s):  
Liana Oliveira ◽  
Alfredo Marquart-Filho ◽  
Gerson Trevilato ◽  
Rodolfo Timoteo ◽  
Maira Mukai ◽  
...  
Keyword(s):  
Pemphigus Vulgaris ◽  
Pemphigus Foliaceus ◽  
Endemic Pemphigus Foliaceus

scholarly journals IgM Deficiency in Autoimmune Blistering Mucocutaneous Diseases Following Various Treatments: Long Term Follow-Up and Relevant Observations

2021 ◽  
Vol 12 ◽  
Author(s):  
A. Razzaque Ahmed ◽  
Merve Aksoy
Keyword(s):  
Autoimmune Diseases ◽  
Pemphigus Vulgaris ◽  
Mucous Membrane Pemphigoid ◽  
Pemphigus Foliaceus ◽  
Ocular Cicatricial Pemphigoid ◽  
Long Term Follow Up ◽  
Health And Disease ◽  
Igm Deficiency

IgM deficiency has been reported in patients with many autoimmune diseases treated with Rituximab (RTX). It has not been studied, in detail, in autoimmune mucocutaneous blistering diseases (AIMBD). Our objectives were: (i) Examine the dynamics of IgM levels in patients with and without RTX. (ii) Influence of reduced serum IgM levels on clinical and laboratory parameters. (iii) Explore the possible molecular and cellular basis for reduced serum IgM levels. This retrospective study that was conducted in a single-center from 2000 to 2020. Serial IgM levels were studied in 348 patients with five AIMBD (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, and ocular cicatricial pemphigoid) and found decreased in 55 patients treated with RTX, IVIG, and conventional immunosuppressive therapy (CIST). Hence the incidence of decreased serum IgM is low. The incidence of decreased IgM in patients treated with RTX was 19.6%, in patients treated with IVIG and CIST, it was 52.8% amongst the 55 patients. IgM levels in the post-RTX group were statistically significantly different from the IVIG group (p&lt;0.018) and CIST group (p&lt;0.001). There were no statistically significant differences between the groups in other clinical and laboratory measures. Decreased serum IgM did not affect depletion or repopulation of CD19+ B cells. Patients in the three groups achieved clinical and serological remission, in spite of decreased IgM levels. Decrease in IgM was isolated, since IgG and IgA were normal throughout the study period. Decreased IgM persisted at the same level, while the patients were in clinical remission, for several years. In spite of persistent decreased IgM levels, the patients did not develop infections, tumors, other autoimmune diseases, or warrant hospitalization. Studies on IgM deficiency in knockout mice provided valuable insights. There is no universally accepted mechanism that defines decreased IgM levels in AIMBD. The data is complex, multifactorial, sometimes contradictory, and not well understood. Nonetheless, data in this study provides novel information that enhances our understanding of the biology of IgM in health and disease.

scholarly journals Endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris: immunoglobulin G heterogeneity detected by indirect immunofluorescence

2004 ◽  
Vol 59 (5) ◽  
pp. 251-256 ◽  
Author(s):  
Valéria Aoki ◽  
Milian H. T. Huang ◽  
Alexandre M. Périgo ◽  
Lígia M. I. Fukumori ◽  
Celina W. Maruta ◽  
...  
Keyword(s):  
Disease Activity ◽  
Indirect Immunofluorescence ◽  
Immunoglobulin G ◽  
Clinical Remission ◽  
Pemphigus Vulgaris ◽  
Pemphigus Foliaceus ◽  
Igg Subclass ◽  
Immunoglobulin G4 ◽  
Endemic Pemphigus Foliaceus ◽  
Active Disease

Pemphigus are autoimmune intraepidermal blistering diseases in which immunoglobulin G (IgG) autoantibodies are directed against desmosomal glycoproteins. The aim of this study was to determine the IgG subclass profile of endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris utilizing indirect immunofluorescence. PATIENTS AND METHODS: Twenty-five patients with pemphigus vulgaris, 25 with endemic pemphigus foliaceus (fogo selvagem), and 25 healthy controls were analyzed by indirect immunofluorescence for circulating autoantibodies (total IgG and its subclasses). RESULTS: Our data revealed a significant correlation (P <.05) of disease activity and autoantibody levels in both forms of pemphigus, i.e., negative titers related to clinical remission, whereas positive results related to active disease. Immunoglobulin G subclass analysis in fogo selvagem demonstrated that in patients in remission, 56% showed positive immunoglobulin G4; in active disease, immunoglobulin G4 was the predominant subclass (100% positive in all cases). The IgG subclass profile in pemphigus vulgaris showed that in patients in remission, only 10% were positive for immunoglobulin G4; in active disease, positivity for immunoglobulin G4 was present in 78% to 88% of the cases. CONCLUSION: Subclass characterization of immunoglobulin G autoantibodies is a useful tool for pemphigus follow-up, since immunoglobulin G4 (IgG4) is the subclass that is closely related to recognition of pathogenic epitopes, and consequently with disease activity. Careful monitoring should be performed for fogo selvagem in clinical remission with a homogeneous IgG4 response, since this may indicate more frequent relapses.

scholarly journals Bullous Skin Diseases: Classical Types of Autoimmune Diseases

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Jan Damoiseaux
Keyword(s):  
Autoimmune Diseases ◽  
Bullous Pemphigoid ◽  
Oral Mucosa ◽  
Skin Diseases ◽  
Pemphigus Vulgaris ◽  
Pemphigus Foliaceus ◽  
Blister Formation ◽  
Koch’S Postulates ◽  
Bullous Skin Diseases ◽  
Koch's Postulates

The prototypic bullous skin diseases, pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid, are characterized by the blister formation in the skin and/or oral mucosa in combination with circulating and deposited autoantibodies reactive with (hemi)desmosomes. Koch’s postulates, adapted for autoimmune diseases, were applied on these skin diseases. It appears that all adapted Koch’s postulates are fulfilled, and, therefore, these bullous skin diseases are to be considered classical autoimmune diseases within the wide and expanding spectrum of autoimmune diseases.

scholarly journals CD146/sCD146 in the Pathogenesis and Monitoring of Angiogenic and Inflammatory Diseases

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 592
Author(s):  
Xavier Heim ◽  
Ahmad Joshkon ◽  
Julien Bermudez ◽  
Richard Bachelier ◽  
Cléa Dubrou ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Cell Adhesion Molecule ◽  
Inflammatory Diseases ◽  
Biological Fluids ◽  
Soluble Form ◽  
Th17 Lymphocytes ◽  
Bowel Diseases ◽  
A Cell ◽  
Inflammatory Bowel ◽  
Inflammatory Autoimmune Diseases

CD146 is a cell adhesion molecule expressed on endothelial cells, as well as on other cells such as mesenchymal stem cells and Th17 lymphocytes. This protein also exists in a soluble form, whereby it can be detected in biological fluids, including the serum or the cerebrospinal fluid (CSF). Some studies have highlighted the significance of CD146 and its soluble form in angiogenesis and inflammation, having been shown to contribute to the pathogenesis of many inflammatory autoimmune diseases, such as systemic sclerosis, mellitus diabetes, rheumatoid arthritis, inflammatory bowel diseases, and multiple sclerosis. In this review, we will focus on how CD146 and sCD146 contribute to the pathogenesis of the aforementioned autoimmune diseases and discuss the relevance of considering it as a biomarker in these pathologies.

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