RESUMO
Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and most severe form of pemphigus, occurring universally, usually between 40 and 60 years of age. It usually begins with blisters and erosions on the oral mucosa, followed by lesions on other mucous membranes and flaccid blisters on the skin, which can be disseminated. There is a clinical variant, pemphigus vegetans, which is characterized by the presence of vegetating lesions in the large folds of the skin. Clinical suspicion can be confirmed by cytological examination, histopathological examination, and direct and indirect immunofluorescence tests. The treatment is performed with systemic corticosteroids, and immunosuppressive drugs may be associated, among them azathioprine and mycophenolate mofetil. More severe cases may benefit from corticosteroids in the form of intravenous pulse therapy, and recent studies have shown a beneficial effect of rituximab, an anti-CD20 immunobiological drug. It is a chronic disease with mortality around 10%, and septicemia is the main cause of death. Patients need long-term and multidisciplinary follow-up.
Assuntos
Pênfigo/diagnóstico , Adulto , Autoanticorpos/imunologia , Desmossomos/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/classificação , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Pênfigo/classificação , Pênfigo/epidemiologia , Pênfigo/terapia , Pele/patologia , Inquéritos e QuestionáriosRESUMO
Abstract: Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and most severe form of pemphigus, occurring universally, usually between 40 and 60 years of age. It usually begins with blisters and erosions on the oral mucosa, followed by lesions on other mucous membranes and flaccid blisters on the skin, which can be disseminated. There is a clinical variant, pemphigus vegetans, which is characterized by the presence of vegetating lesions in the large folds of the skin. Clinical suspicion can be confirmed by cytological examination, histopathological examination, and direct and indirect immunofluorescence tests. The treatment is performed with systemic corticosteroids, and immunosuppressive drugs may be associated, among them azathioprine and mycophenolate mofetil. More severe cases may benefit from corticosteroids in the form of intravenous pulse therapy, and recent studies have shown a beneficial effect of rituximab, an anti-CD20 immunobiological drug. It is a chronic disease with mortality around 10%, and septicemia is the main cause of death. Patients need long-term and multidisciplinary follow-up.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Pênfigo/diagnóstico , Pele/patologia , Autoanticorpos/imunologia , Inquéritos e Questionários , Pênfigo/classificação , Pênfigo/terapia , Pênfigo/epidemiologia , Imunoglobulinas Intravenosas/uso terapêutico , Desmossomos/imunologia , Diagnóstico Diferencial , Imunossupressores/classificação , Imunossupressores/uso terapêutico , Imunoterapia/métodosRESUMO
Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1's effects on liver by comparing wild-type controls, heterozygous igf1+/-, and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage.
Assuntos
Proteínas de Fase Aguda/metabolismo , Regulação da Expressão Gênica , Hepatite/metabolismo , Mediadores da Inflamação/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/metabolismo , Receptores de Somatomedina/metabolismo , Proteínas de Fase Aguda/genética , Animais , Caderinas/genética , Caderinas/metabolismo , Cruzamentos Genéticos , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Desmossomos/imunologia , Desmossomos/metabolismo , Desmossomos/patologia , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Perfilação da Expressão Gênica , Hepatite/imunologia , Hepatite/patologia , Hepatite/prevenção & controle , Injeções Subcutâneas , Fator de Crescimento Insulin-Like I/administração & dosagem , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/uso terapêutico , Peroxidação de Lipídeos , Fígado/imunologia , Fígado/patologia , Masculino , Camundongos , Camundongos Transgênicos , Estresse Oxidativo , Receptores de Somatomedina/genética , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismoRESUMO
Pemphigus is an autoimmune skin disease that can present in a variety of forms and can prove challenging to manage and treat. An overview of the condition in Mexico is presented. Emphasis is placed on management of the condition, with description of the most commonly used treatments (glucocorticoids, azathioprine), the second line therapies (cyclosporine and mycophenolate mofetil), and additional alternative treatments (cyclophosphamide and dapsone).
Assuntos
Pênfigo/tratamento farmacológico , Corticosteroides/uso terapêutico , Azatioprina/uso terapêutico , Antagonistas Colinérgicos/uso terapêutico , Dapsona/uso terapêutico , Desmossomos/imunologia , Humanos , Imunossupressores/uso terapêutico , Queratinócitos/imunologia , México , Niacinamida/uso terapêutico , Pênfigo/imunologia , Pênfigo/patologia , Tetraciclina/uso terapêuticoRESUMO
Most of the clinical, histological and immunohistological features of fogo selvagem resemble those of idiopathic pemphigus foliaceus (PF). Both diseases are clinically characterized by small flaccid bullae evolving into to scaly and crusted lesions, sometimes with pustules, mainly in seborrheic areas of the skin. Mucosal surfaces are mostly spared. The main histologic feature of endemic pemphigus foliaceus is a subcorneal acantholytic blister. Standard immunofluorescence studies demonstrate intercellular IgG deposits throughout the entire epidermis. These IgG antibodies are mainly of the IgG4-subclass. Almost all patients have circulating IgG-autoantibodies in their serum directed against stratified epithelial desmosomes. The fogo selvagem autoantibodies and the PF antibodies are directed against the 160 kD desmosomal glycoprotein desmoglein 1 which together with plakoglobin (85 kD) forms a complex of adhesion proteins with desmosomes of stratified epithelia. Fogo selvagem occurs in endemic foci in some areas of Brazil and possibly in neighbouring South American countries, very often in children, adolescents and young adults. The etiology of fogo selvagem is still unknown. The frequent association with insect bites has lead to the concept of fogo selvagem being a transmissible disease with acquired immunity in adulthood. However, the infectious agent and possible vectors have not yet been identified.
Assuntos
Pênfigo/etiologia , Adolescente , Adulto , Autoanticorpos/imunologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Brasil , Criança , Proteínas do Citoesqueleto/imunologia , Desmogleína 1 , Desmogleínas , Desmoplaquinas , Desmossomos/imunologia , Desmossomos/patologia , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imunoglobulina G/análise , Pênfigo/imunologia , Pênfigo/patologia , Pele/imunologia , Pele/patologia , gama CateninaRESUMO
Recently, it has been shown that desmoglein, pemphigus foliaceus target antigen, and a 130-kD pemphigus vulgaris antigen belong to the cadherin family of cell adhesion molecules. We tried to determine whether desmocollins I/II, other cadherin-like transmembranous glycoproteins present in desmosomes, are also recognized by pemphigus autoantibodies of the IgG class. We examined 16 pemphigus vulgaris sera, 15 pemphigus foliaceus sera, 15 Brazilian pemphigus foliaceus sera, five bullous pemphigoid sera, and 65 normal sera. Four (25%) pemphigus vulgaris sera, one (7%) pemphigus foliaceus serum, eight (53%) Brazilian pemphigus foliaceus sera, and three (5%) normal sera reacted with desmocollins I/II on immunoblots of bovine desmosome preparation. The affinity-purified desmocollins I/II pemphigus autoantibodies were shown to bind the epidermal cell surface by indirect immunofluorescence. Immunoblot analysis revealed one pemphigus vulgaris serum, one Brazilian pemphigus foliaceus serum, and one normal serum recognizing a recombinant protein produced by a desmocollin cDNA clone. Moreover, immunoblot analysis of reactivity of a Brazilian pemphigus foliaceus serum with recombinant proteins produced by deletion mutants of the desmocollin cDNA clone showed that the extracellular portion of desmocollin is immunogenic in this pemphigus patient. We conclude that desmocollins I/II are recognized by certain sera from patients with various types of pemphigus, particularly Brazilian pemphigus foliaceus. However, the significance of this reactivity remains to be defined.
Assuntos
Proteínas do Citoesqueleto/sangue , Pênfigo/sangue , Animais , Anticorpos/sangue , Antígenos/análise , Bovinos , Cromatografia de Afinidade , Proteínas do Citoesqueleto/análise , Desmocolinas , Desmogleínas , Desmoplaquinas , Desmossomos/química , Desmossomos/imunologia , Epiderme/imunologia , Humanos , Immunoblotting , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Pênfigo/imunologia , Proteínas Recombinantes/análise , Proteínas Recombinantes/sangueRESUMO
We investigated the Brazilian pemphigus foliaceus (BPf) antigen applying the immunoblotting method to two different antigen sources using 27 patients' sera. Twelve BPf sera reacted specifically with a 150 kD protein in extract of dispase separated human epidermis, while 18 sera yielded a similar protein band in bovine muzzle desmosomal preparation. The diversity of staining intensities between the two samples suggested the heterogeneity of BPf antigens in terms of epitopes. Japanese sporadic pemphigus foliaceus (Pf) sera showed similar results but Japanese pemphigus vulgaris (Pv) sera recognized different antigens of 130 kD or 135 kD, suggesting that BPf is similar to Japanese Pf but is distinct from Pv in respect to the antigenic substance. Furthermore, the present study showed that immunoblot analysis using different antigen sources should be a valuable tool to determine clinical types of pemphigus.