RESUMO
Desmogleins are involved in cell adhesion conferring structural skin integrity. However, their role in inflammation has been barely studied, and whether desmoglein-4 modulates psoriasis lesions is completely unknown. In this study, we assessed the impact of desmoglein-4 deficiency on the severity of imiquimod (IMQ)-induced skin inflammation and psoriasiform lesions. To this end, desmoglein-4-/- Oncins France Colony A (OFA) with Sprague-Dawley (SD) genetic background were used. Additionally, human RNA-Seq datasets from psoriasis (PSO), atopic dermatitis (AD), and a healthy cohort were analyzed to obtain a desmosome gene expression overview. OFA rats displayed an intense skin inflammation while SD showed only mild inflammatory changes after IMQ treatment. We found that IMQ treatment increased CD3+ T cells in skin from both OFA and SD, being higher in desmoglein-4-deficient rats. In-depth transcriptomic analysis determined that PSO displayed twofold less DSG4 expression than healthy samples while both, PSO and AD showed more than three-fold change expression of DSG3 and DSC2 genes. Although underlying mechanisms are still unknown, these results suggest that the lack of desmoglein-4 may contribute to immune-mediated skin disease progression, promoting leukocyte recruitment to skin. Although further research is needed, targeting desmoglein-4 could have a potential impact on designing new biomarkers for skin diseases.
Assuntos
Desmogleínas/deficiência , Psoríase/metabolismo , Pele/metabolismo , Animais , Complexo CD3/metabolismo , Estudos de Casos e Controles , Quimiotaxia de Leucócito , Desmogleínas/genética , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Humanos , Imiquimode , Mediadores da Inflamação/metabolismo , Psoríase/induzido quimicamente , Psoríase/imunologia , Psoríase/patologia , Ratos Sprague-Dawley , Ratos Transgênicos , Pele/imunologia , Pele/patologia , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Abstract: Fogo selvagem or endemic pemphigus foliaceus is an autoimmune acantholytic anti-cadherin bullous disease that primarily affects seborrheic areas, which might disseminate. Brazil has the world's largest number of patients, mainly in the Central-West region, but the disease has also been reported in other South American countries. It affects young people and adults who have been exposed to rural areas, with occurrence of familial cases. Anti-desmoglein-1 autoantibodies are directed against desmosomal structures, with loss of adhesion of the upper layers of the epidermis, causing superficial blisters. The etiology is multifactorial and includes genetic, immune, and environmental factors, highlighting hematophagous insect bites; drug-related factors are occasionally involved. Flaccid blisters readily rupture to yield erosive-crusty lesions that sometimes resemble seborrheic dermatitis, actinic keratosis, and chronic cutaneous lupus erythematosus. The clinical presentation varies from localized to disseminated lesions. Clinical suspicion should be confirmed with histopathological and immunofluorescence tests, among others. The progression is usually chronic, and therapy varies according to clinical presentation, but generally requires systemic corticosteroid therapy associated with adjuvant immunosuppressive treatment to decrease the adverse effects of corticosteroids. Once the disease is under control, many patients remain stable on low-dose medication, and a significant proportion achieve remission.
Assuntos
Humanos , Pênfigo/etiologia , Pênfigo/epidemiologia , Doenças Endêmicas , Autoanticorpos/imunologia , Brasil/epidemiologia , Fotografação , Pênfigo/diagnóstico , Pênfigo/patologia , Desmogleínas/imunologiaRESUMO
Fogo selvagem or endemic pemphigus foliaceus is an autoimmune acantholytic anti-cadherin bullous disease that primarily affects seborrheic areas, which might disseminate. Brazil has the world's largest number of patients, mainly in the Central-West region, but the disease has also been reported in other South American countries. It affects young people and adults who have been exposed to rural areas, with occurrence of familial cases. Anti-desmoglein-1 autoantibodies are directed against desmosomal structures, with loss of adhesion of the upper layers of the epidermis, causing superficial blisters. The etiology is multifactorial and includes genetic, immune, and environmental factors, highlighting hematophagous insect bites; drug-related factors are occasionally involved. Flaccid blisters readily rupture to yield erosive-crusty lesions that sometimes resemble seborrheic dermatitis, actinic keratosis, and chronic cutaneous lupus erythematosus. The clinical presentation varies from localized to disseminated lesions. Clinical suspicion should be confirmed with histopathological and immunofluorescence tests, among others. The progression is usually chronic, and therapy varies according to clinical presentation, but generally requires systemic corticosteroid therapy associated with adjuvant immunosuppressive treatment to decrease the adverse effects of corticosteroids. Once the disease is under control, many patients remain stable on low-dose medication, and a significant proportion achieve remission.
Assuntos
Doenças Endêmicas , Pênfigo/epidemiologia , Pênfigo/etiologia , Autoanticorpos/imunologia , Brasil/epidemiologia , Desmogleínas/imunologia , Humanos , Pênfigo/diagnóstico , Pênfigo/patologia , FotografaçãoRESUMO
Bullous pemphigoid is a blistering autoimmune disease characterized by two hemidesmosomal proteins (anti-BP180 and 230). Pemphigus, by contrast, is characterized by two autoantibodies (anti-desmoglein 1 and 3). Coexistence of autoantibodies of bullous pemphigoid and pemphigus in a patient is rare. A 25-year-old male patient was admitted to our hospital, reporting a 3-month history of multiple papules, vesicles, and erosions over an extensive erythema on the entire body. Laboratory tests showed high levels of serum IgE, anti-BP180 antibodies, and anti-desmoglein 1 and 3. Histopathologic and immunopathologic features were characterized by bullous pemphigoid. No improvement was seen with systemic corticosteroid therapy, however, pulse corticosteriod therapy combined with methylprednisolone, immunosuppressants, immunomodulators, and plasmapheresis led to the recovery of his condition with numerous milia.
Assuntos
Desmogleínas/imunologia , Imunoglobulina E/sangue , Ceratose/imunologia , Ceratose/patologia , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/patologia , Adulto , Autoanticorpos/sangue , Autoantígenos/sangue , Biópsia , Glucocorticoides/uso terapêutico , Humanos , Ceratose/tratamento farmacológico , Masculino , Metilprednisolona/uso terapêutico , Colágenos não Fibrilares/sangue , Penfigoide Bolhoso/tratamento farmacológico , Úlcera por Pressão/patologia , Pele/patologia , Colágeno Tipo XVIIRESUMO
Background: Antibodies against Leishmania peptides (Lbr-peps) and desmogleins (Dsgs) have been reported in pemphigus foliaceus (PF) and leishmaniasis patients, respectively. We aimed to compare serological and genetic features in a Brazilian region endemic for American tegumentary leishmaniasis (ATL) and pemphigus. Methods: Commercial anti-Dsg ELISA and in-house ELISA with Lbr-peps were used to determine the serological profile, in addition to immunoblotting (IB) and indirect immunofluorescence (IIF) assays. HLA-DRB1 and -DQA1/DQB1 alleles were characterized by PCR combined with sequence-specific oligonucleotide probes (PCR-SSOP). The serological and genetic profiles were compared using 78 PF, 62 pemphigus vulgaris (PV) and 58 ATL patients against 163 and 1592 healthy controls, respectively. Results: Some ATL patients showed positive results for anti-Dsg1 and/or anti-Dsg3 antibodies. They also revealed 130, 160 and/or 230 kDa epidermal peptides in IB. Moreover, some ATL samples exhibited pemphigus or a bullous pemphigoid pattern in IIF. ELISA and IB assays showed Lbr-peps in pemphigus patients. HLA-DQA1*01 and -DQA1*01:02 were protective and susceptibility alleles for ATL, respectively, but the opposite for pemphigus. Conclusions: Anti-Dsgs in ATL may represent epiphenomena. Anti-Lbr-pep antibodies in pemphigus suggest a previous infection. A differential association of the HLA profile may contribute to the lack of co-association between pemphigus and ATL.
Assuntos
Desmogleínas/sangue , Leishmaniose Cutânea/diagnóstico , Pênfigo/diagnóstico , Adulto , Alelos , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Cadeias beta de HLA-DQ/sangue , Cadeias HLA-DRB1/sangue , Humanos , Immunoblotting , Leishmaniose Cutânea/genética , Masculino , Pessoa de Meia-Idade , Pênfigo/genéticaRESUMO
Abstract: Bullous pemphigoid is a blistering autoimmune disease characterized by two hemidesmosomal proteins (anti-BP180 and 230). Pemphigus, by contrast, is characterized by two autoantibodies (anti-desmoglein 1 and 3). Coexistence of autoantibodies of bullous pemphigoid and pemphigus in a patient is rare. A 25-year-old male patient was admitted to our hospital, reporting a 3-month history of multiple papules, vesicles, and erosions over an extensive erythema on the entire body. Laboratory tests showed high levels of serum IgE, anti-BP180 antibodies, and anti-desmoglein 1 and 3. Histopathologic and immunopathologic features were characterized by bullous pemphigoid. No improvement was seen with systemic corticosteroid therapy, however, pulse corticosteriod therapy combined with methylprednisolone, immunosuppressants, immunomodulators, and plasmapheresis led to the recovery of his condition with numerous milia.
Assuntos
Humanos , Masculino , Adulto , Imunoglobulina E/sangue , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/patologia , Desmogleínas/imunologia , Ceratose/imunologia , Ceratose/patologia , Pele/patologia , Autoanticorpos/sangue , Autoantígenos/sangue , Biópsia , Metilprednisolona/uso terapêutico , Penfigoide Bolhoso/tratamento farmacológico , Colágenos não Fibrilares/sangue , Úlcera por Pressão/patologia , Glucocorticoides/uso terapêutico , Ceratose/tratamento farmacológicoRESUMO
Desmoglein 4 (DSG4) has an important role in the development of wool traits in domestic animals. The full-length DSG4 gene, which contains 3918 bp, a complete open-reading-frame, and encodes a 1040-amino acid protein, was amplified from Liaoning cashmere goat. The sequence was compared with that of DSG4 from other animals and the results show that the DSG4 coding region is consistent with interspecies conservation. Thirteen single-nucleotide polymorphisms (SNPs) were identified in a highly variable region of DSG4, and one SNP (M-1, G>T) was significantly correlated with white and black coat color in goat. Haplotype distribution of the highly variable region of DSG4 was assessed in 179 individuals from seven goat breeds to investigate its association with coat color and its differentiation among populations. However, the lack of a signature result indicates DGS4 haplotypes related with the color of goat coat.
Assuntos
Desmogleínas/genética , Cabras/metabolismo , Cor de Cabelo/genética , Polimorfismo de Nucleotídeo Único , Animais , Cabras/genética , Haplótipos , Filogenia , Análise de Sequência de RNARESUMO
The desmoglein 4 (DSG4) gene is a potential candidate in the search for genes that may affect wool traits, because of its function. This study aimed to screen for polymorphisms in partial exon 16 and 3êUTR of the sheep desmoglein 4 DSG4 gene, and to test its possible association with wool length and crimp associated with fur. Overall, 326 sheep were scanned via single-strand conformational polymorphism assay, through three pairs of primers. The breeds included Tan, Han, and TanxHan from China, Polled Dorset from Australia, and Suffolk from Britain genotypes AA, BB, and AB for primer2 and genotypes DD, EE, and DE for primer3 were detected in native breeds. Six SNPs and 3-bp insertion/deletions were found in exon 16, of which 4 lead to amino acid substitutions. In addition, 1 SNP was found in 3êUTR. The DSG4 genotype was found to be strongly associated with all wool traits that were considered in this study (P < 0.01). Sheep with the genotype MM had a higher least square mean compared to sheep with the genotype WW or WM with respect to birth scapular wool length (P < 0.01), crimp number of birth scapular wool crimp (P < 0.01), crimp number of weaning scapular wool crimp (P < 0.01), and crimp number of weaning rump wool crimp (P < 0.01, P < 0.05). In conclusion, our study is the first to demonstrate that the DSG4 gene may be a candidate, or major gene, which influences important wool traits.
Assuntos
Desmogleínas/genética , Estudos de Associação Genética , Desequilíbrio de Ligação , Fenótipo , Característica Quantitativa Herdável , Ovinos/genética , Lã/crescimento & desenvolvimento , Animais , Frequência do Gene , Genótipo , Haplótipos , Polimorfismo Genético , Análise de Sequência de DNARESUMO
It is well established that autoantibodies against desmoglein 3 and desmoglein 1 (Dsg1) are relevant in the pathogenesis of pemphigus vulgaris and pemphigus foliaceus, including its endemic form fogo selvagem (FS). Isolated reports have shown that in certain patients with these diseases, autoantibodies against other desmosomal cadherins and E-cadherin may also be present. The goal of this investigation was to determine whether FS patients and normal individuals living in endemic areas possess autoantibodies against other desmosomal cadherins and E-cadherin. By testing a large number of FS and endemic control sera by ELISA, we found a consistent and specific autoantibody response against Dsg1 and other keratinocyte cadherins in these individuals, which is quite different from healthy individuals from the United States (US controls). Overall, the highest correlations among the autoantibody responses tested were in the endemic controls, followed by FS patients, and lowest in the US controls. These findings suggest that multiple, perhaps cross-reactive, keratinocyte cadherins are recognized by FS patients and endemic controls.
Assuntos
Autoanticorpos/imunologia , Caderinas de Desmossomos/imunologia , Imunoglobulina G/imunologia , Queratinócitos/imunologia , Pênfigo/imunologia , Adulto , Brasil , Caderinas/genética , Caderinas/imunologia , Reações Cruzadas/imunologia , Desmogleína 1/genética , Desmogleína 1/imunologia , Desmogleína 2/genética , Desmogleína 2/imunologia , Desmogleína 3/genética , Desmogleína 3/imunologia , Desmogleínas/genética , Desmogleínas/imunologia , Caderinas de Desmossomos/genética , Humanos , Curva ROC , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Estados UnidosRESUMO
El pénfigo vulgar y el pénfigo foliáceo son enfermedades ampollosas autoinmunes mediadas por autoanticuerpos dirigidos contra proteínas de los desmosomas, las desmogleínas 1 y 3. Están asociadas con moléculas del complejo mayor de histocompatibilidad (HLA) que por su estructura tienen la capacidad de presentar péptidos antigénicos de las desmogleínas. En los individuos afectados se han descrito la presencia de linfocitos T y B autorreactivos y alteraciones en la regulación del sistema inmune con desequilibrio de las respuestas Th1/Th2. No se conocen con precisión los mecanismos de daño pero la investigación actual indica que los anticuerpos tienen un papel patogénico, inician diferentes cascadas de señalización que provocan la acantólisis y apoptosis de los queratinocitos. El conocimiento de la inmunopatogenia de las enfermedades ampollosas autoinmunes ha permitido el desarrollo y la puesta en práctica de nuevas alternativas terapéuticas.
Pemphigus vulgaris and pemphigus foliaceus are autoimmune blistering diseases mediated by antibodies against desmosomal proteins. They are strongly associated with major histocompatibility complex alleles with the ability to present antigenic peptides of desmogleins. In the affected individuals the presence of auto-reactive T and B lymphocytes, and alterations in the immune system regulation with imbalance of the Th1/Th2 responses have been described. Damage mechanisms are not yet precisely known but current investigation indicates that antibodies play an important pathogenic role: they start different signaling cascades that lead to acantholysis and apoptosis of keratinocytes. Better knowledge of the pathogenesis of autoimmune blistering diseases has been the basis for the development and implementation of new therapeutic approaches.
Assuntos
Humanos , Acantólise , Desmogleínas , Desmossomos , Dermatopatias Vesiculobolhosas , Pênfigo , Alergia e ImunologiaRESUMO
Lactation deficiency may have important consequences on infant health, particularly in populations of low socioeconomic status. The OFA hr/hr (OFA) strain of rats, derived from Sprague-Dawley (SD) rats, has deficient lactation and is a good model of lactation failure. We examined the reproductive performance and hormonal profiles in OFA and SD strains to determine the cause(s) of the lactation failure of the OFA strain. We measured hormonal (PRL, GH, gonadotropins, oxytocin, and progesterone) levels by RIA in cycling, pregnant, and lactating rats and in response to suckling. Dopaminergic metabolism was assessed by determination of mediobasal hypothalamic dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations by HPLC and tyrosine hydroxylase expression by immunocytochemistry and western blot. OFA rats have normal fertility but 50% of the litters die of malnutrition on early lactation; only 6% of the mothers show normal lactation. The OFA rats showed lower circulating PRL during lactation, increased hypothalamic dopamine and DOPAC, and impaired milk ejection with decreased PRL and oxytocin response to suckling. Before parturition, PRL release and lactogenesis were normal, but dopaminergic metabolism was altered, suggesting activation of the dopaminergic system in OFA but not in SD rats. The number of arcuate and periventricular neurons expressing tyrosine hydroxylase was higher in SD rats, but hypothalamic expression of TH was higher in OFA rats at the end of pregnancy and early lactation. These results suggest that the OFA rats have impaired PRL release linked with an augmented dopaminergic tone which could be partially responsible for the lactational failure.
Assuntos
Lactação/fisiologia , Prenhez/metabolismo , Prolactina/sangue , Ácido 3,4-Di-Hidroxifenilacético/análise , Animais , Western Blotting , Caseínas/análise , Cromatografia Líquida de Alta Pressão , Desmogleínas/genética , Dopamina/análise , Feminino , Hipotálamo Médio/química , Lactose/análise , Glândulas Mamárias Animais/química , Glândulas Mamárias Animais/patologia , Modelos Animais , Gravidez , Proestro/metabolismo , Ratos , Ratos Mutantes , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/análiseRESUMO
UNLABELLED: 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.
Assuntos
Autoanticorpos/sangue , Imunoglobulina G/sangue , Pênfigo/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Desmogleínas/imunologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Pênfigos são enfermidades auto-imunes bolhosas intraepidérmicas, onde auto-anticorpos IgG se dirigem contra glicoproteínas desmossomais. O objetivo deste estudo foi determinar o perfil de subclasses de imunoglubulina G no pênfigo foliáceo endêmico (fogo selvagem) e no pênfigo vulgar através da imunofluorescência indireta. MÉTODOS: Vinte e cinco doentes de pênfigo foliáceo endêmico (fogo selvagem), 25 de pênfigo vulgar e 25 controles sadios foram analisados através da imunofluorescência indireta, com respeito aos auto-anticorpos circulantes (imunoglobulina G total e subclasses). RESULTADOS: Nossos dados mostram uma correlação estatisticamente significativa (p<0.05) entre atividade da doença e títulos de auto-anticorpos circulantes em ambas as formas de pênfigo, ou seja, títulos negativos relacionaram-se com remissão clínica, enquanto resultados positivos correlacionaram-se com doença em atividade. A análise de subclasses de IgG mostrou que 56% dos doentes de fogo selvagem em remissão apresentaram apenas IgG4 positiva; na doença ativa, IgG4 foi a subclasse predominante, sendo positiva em 100% dos casos. Nos doentes de pênfigo vulgar, apenas 10% dos doentes em remissão apresentaram positividade exclusiva para IgG4; na doença em atividade, IgG4 esteve presente em 78-83,3% dos casos. CONCLUSÕES: A caracterização de subclasses de imunoglobulina G consiste em um instrumento de grande valia no seguimento de doentes de pênfigo, uma vez que a IgG4 é a subclasse intimamente relacionada com o reconhecimento de epítopos patogênicos, e consequentemente com atividade da enfermidade. No fogo selvagem em remissão com uma resposta homogênea 'as custas de IgG4, uma monitoração cuidadosa deve ser realizada, uma vez que isto pode significar uma maior chance de reativação.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autoanticorpos/sangue , Imunoglobulina G/sangue , Pênfigo/imunologia , Estudos de Casos e Controles , Desmogleínas/imunologia , Técnica Indireta de Fluorescência para Anticorpo , SeguimentosRESUMO
Eicosatrienoic acid (ETA 5,8,11, n-9) is abnormally increased by essential fatty acid deficiency (EFAD), a condition associated with alterations of cell proliferation and differentiation. In comparison to certain EFAs, addition of ETA at a low concentration resulted in a reduction in the expression of the cell-cell adhesion molecule, E-cadherin, and to a lesser degree, of desmoglein, along with increased invasion of Matrigel by human squamous cell carcinoma (SCC) cells in vitro. At higher concentrations, ETA stimulated the growth of SCC cells. As previously shown, n-6 EFAs (mainly 18:3 n-6, GLA), up-regulated the expression of E-cadherin and desmoglein. This is the first report showing that the abnormal 20:3 n-9 (Mead's acid) is a down regulator of antimetastatic E-cadherin and desmoglein expression.
Assuntos
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Caderinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas do Citoesqueleto/metabolismo , Ácido 8,11,14-Eicosatrienoico/farmacologia , Bisbenzimidazol/metabolismo , Western Blotting , Caderinas/imunologia , Moléculas de Adesão Celular , Divisão Celular , Desmogleínas , Desmoplaquinas , Relação Dose-Resposta a Droga , Humanos , Imuno-Histoquímica , Células Tumorais Cultivadas , Ácido gama-Linolênico/metabolismoRESUMO
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
The epidermal blistering disease, pemphigus vulgaris (PV), is caused by circulating autoantibodies that react with a desmosomal glycoprotein desmoglein (Dsg3). This antigen is expressed only in stratified epithelial tissues. Here we show that the simple epithelial canine kidney cell line, MDCK, expresses at least two desmoglein isoforms recognised by different monoclonal antibodies. One of these isoforms is a 130 x 10(3) M(r) polypeptide that is recognised by both PV autoantisera and a monoclonal antibody reactive with a cytoplasmic domain of human Dsg3. Antibodies in PV sera bind to the surface of MDCK cells but not cause loss of intercellular adhesion. This is the first demonstration of the expression of a polypeptide related to human PV antigen by a simple epithelial cell type.
Assuntos
Caderinas/análise , Proteínas do Citoesqueleto/análise , Animais , Anticorpos Monoclonais , Western Blotting , Caderinas/imunologia , Bovinos , Adesão Celular , Moléculas de Adesão Celular/análise , Linhagem Celular , Proteínas do Citoesqueleto/imunologia , Desmogleína 3 , Desmogleínas , Desmoplaquinas , Cães , Eletroforese em Gel de Poliacrilamida , Epiderme/ultraestrutura , Epitélio , Imunofluorescência , Humanos , Rim , Microscopia Imunoeletrônica , Peso Molecular , Pênfigo/imunologiaRESUMO
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
Desmosome junctions are found in epithelial tissues. They both link cells externally and anchor cytoplasmic intermediate filaments to the plasma membrane. Quantitative and qualitative abnormalities in intercellular junctions have been described in a broad spectrum of human and animal cancers. Current efforts are aimed at exploring the possibility that some of these defects may account for the hallmarks of malignancy, namely tumour invasion and metastasis. Desmosomes are constituted by several proteins, one of them is desmoglein-1 (DG-1), a transmembrane glycoprotein who glycosylated portion is major component of the adhesion mediating desmoglia. In order to know the similarity between tissue DG-1 and cultured renal cells DG-1 was used antisera raised against DG-1 to identify cross-reacting components. Anti DG-1 antibodies stained cell-cell boundaries in a punctate fashion in epithelial tissue and on densely grown monolayers of renal cells. Radioimmunoprecipitation and immunoelectrotransference show positive reaction with anti DG-1 antibodies with desmosomes obtained from epithelial tissue and renal cells monolayers, but last one was less positive. Results suggest some minor differences between DG-1 extracted from diverse sources but they have a commun immunodominant epitope.