Pénfigo Foliáceo con desafío terapéutico / Pemphigus foliaceus with therapeutic challenge

Resumen El pénfigo foliáceo es una enfermedadversículo ampollar autoinmune poco frecuente,caracterizada histopatológicamente por acantólisis, inducida por la presencia de autoanticuerpos frente a la desmogleína 1. El desprendimiento se localiza en los estratos más superficiales de la epidermis produciendo ampollas frágiles y erosiones. Se clasifica en endémico y no endémico o esporádico. Dentro de este último podemos encontrar una variedad localizada y una generalizada. Presentamos el caso de un paciente, con diagnósticoy confirmación histopatológica de pénfigo foliáceo y realizamos una breve revisión de la literatura.

Summary Foliaceus pemphigus is an infrequent autoimmune blistering verse disease characterized histopathologically by acantholysis, induced by the presence of autoantibodies against desmoglein 1. The detachment is located in the most superficial layers of the epidermis produces fragile blisters and erosions. It is classified as endemic, and not endemic or sporadic. Within the latter we can find a localized and a generalized variety. Presents the case of a patient, diagnosis and histopathological confirmation of a paper and makes a brief review of the literature.

Oxidative stress in patients with endemic pemphigus foliaceus and healthy subjects with anti-desmoglein 1 antibodies

Abstract: Background: Previous studies have shown oxidative stress in pemphigus vulgaris and pemphigus foliaceus, nevertheless, it remains unknown whether a similar response is characteristic of endemic pemphigus foliaceus in Peru. Objectives: To determine the oxidative stress response in endemic pemphigus foliaceus patients and subjects with positive for anti-desmoglein1 antibodies (anti-dsg1) from endemic areas of Peru. Subjects and Methods: This is a cross-sectional study. The study population included 21 patients with Endemic Pemphigus foliaceus and 12 healthy subjects with anti-dsg1 antibodies from the Peruvian Amazon (Ucayali), as well as 30 healthy control subjects. Malondialdehyde, an indicator of lipid peroxidation by free radicals, was measured in serum. Results: We collected 21 cases of endemic pemphigus foliaceus, 15 of them with active chronic disease and 6 in clinical remission. Serum malondialdehyde values in patients with chronic active evolution and healthy subjects with anti-dsg1 antibodies were statistically higher than those of healthy controls (p<0.001). There was no significant difference between serum values of localized and generalized clinical forms. Study limitations: The main limitation of this present study is the small number of patients with endemic pemphigus and healthy subjects positive for desmoglein 1 antibodies. Conclusions: The increased serum levels of malondialdehyde in patients with chronic active endemic pemphigus foliaceus and healthy subjects from endemic areas with anti-dsg1 antibodies may suggest a contribution of systemic lipid peroxidation in the pathogenesis of endemic pemphigus foliaceus.

Paraneoplastic Pemphigus Associated with a Malignant Thymoma: A Case of Persistent and Refractory Oral Ulcerations Following Thymectomy

Paraneoplastic pemphigus is a rare, life-threatening autoimmune mucocutaneous blistering disease associated with underlying neoplasia, commonly lymphoproliferative tumors. Herein we report a case of paraneoplastic pemphigus with a unique autoantibody profile associated with a malignant thymoma. A 56-year-old female patient presented with relapsing oral ulcerations accompanied by erythematous papules and patches on her extremities for 2 months. Skin and mucosal biopsies identified interface dermatitis with lichenoid lymphocytic infiltration in the upper dermis. Immunoblotting and enzyme-linked immunosorbent assays revealed that the patient had multiple autoantibodies against desmoglein 1, desmocollin 1, 2, 3, laminin gamma-1, envoplakin, and periplakin. The skin lesions completely healed following thymectomy and systemic corticosteroid therapy, but the oral ulcerations persisted through a follow-up period of over 2 years.

Avaliação das alterações de desmogleína 1 em carcinoma epidermoide de esôfago / [Evaluation of changes in desmoglein 1 in esophageal squamous cell carcinoma]

O câncer de esôfago (CE) é um dos dez tipos de tumores mais frequentes e apresenta uma sobrevida em cinco anos inferior a 20% no Brasil e no mundo. Esta alta letalidade está relacionada ao diagnóstico tardio da doença, o que resulta em um tratamento pouco eficaz. Dentre os diferentes tipos histológicos de CE, o carcinoma epidermóide de esôfago (CEE) corresponde a mais de 80% dos casos de câncer de esôfago no Brasil. Frente a tal panorama, a identificação de potenciais biomarcadores que auxiliem no diagnóstico precoce de CEE é fundamental. Diversos trabalhos têm sido desenvolvidos com o objetivo de elucidar o papel das alterações epigenéticas na iniciação e progressão tumoral, e em estudo do nosso grupo, foi observado que alterações no padrão de metilação do DNA são comuns em CEE. As principais vias celulares afetadas foram as de componentes inflamatórios e adesão/diferenciação celular. Dentro desta última via, destacou-se o gene Desmogleína 1 (DSG1), que codifica uma caderina desmossomal de mesmo nome, já relacionada à diferenciação celular em pele. Desta forma, este trabalho teve como objetivo avaliar a presença de alterações de DSG1 em CEE. Nas análises realizadas em amostras humanas, observamos que os tumores apresentam uma hipermetilação da região promotora e menores níveis de expressão gênica de DSG1 em comparação ao tecido adjacente não tumoral pareado. Além disso, menores níveis de metilação foram observados em indivíduos com idade acima da mediana e tumores moderadamente diferenciados...

Esophageal cancer (EC) is one of the ten most frequent tumors worldwide and in Brazil, showing a five-year overall survival lower than 20%. Such a high lethality is directly associated with a late diagnosis, which results in a poor treatment. Among the different histological subtypes of EC, esophageal squamous cell carcinoma (ESCC) corresponds to more than 80% of the cases. Based on this, the identification of biomarkers that could anticipate ESCC diagnosis is of utmost importance. Several studies have tried to elucidate the role of epigenetic alterations on tumor initiation and progression and our group has already shown that alterations of DNA methylation patterns are common events in ESCC. Among the cellular pathways found to be altered in this study, inflammatory components and cell adhesion and differentiation were the most significant. One of the genes found to be hypermethylated in tumors was Desmoglein 1 (DSG1), which encodes a desmosomal protein and has already been implicated in cellular differentiation in skin keratinocytes. Therefore, the main objective of this study was to evaluate the presence of DSG1 molecular alterations in ESCC. The evaluation of human samples showed that ESCC presents DSG1 hypermethylation and a downregulation of its expression in comparison with the paired non-tumor surrounding tissue. Also, lower DSG1 methylation levels were observed in moderately differentiated tumors and in the tumor tissue of older individuals. DSG1 promoter methylation in tumors was also found to be a prognostic factor in ESCC, with individuals with high levels showing a mean overall survival of 6 months, while patients that presented low methylation levels showed a mean overall survival of 15.5 months...

The value of trichoscopy in the differential diagnosis of scalp lesions in pemphigus vulgaris and pemphigus foliaceus

BACKGROUND: Trichoscopy is becoming increasingly popular in diagnosing hair and scalp diseases. Scalp involvement in pemphigus is common. The scalp may be the first or only site of clinical manifestation of the disease. OBJECTIVE: The aim of this study was to analyze whether trichoscopy may be useful in aiding differential diagnosis of scalp lesions in patients with pemphigus vulgaris and pemphigus foliaceus. METHODS: Trichoscopy was performed in 19 patients with scalp lesions in the course of pemphigus (9 patients with pemphigus vulgaris and 10 with pemphigus foliaceus). In all patients, the diagnosis of scalp pemphigus was confirmed by histopathology. The working magnification was 20-fold and 70-fold. RESULTS: The most frequently observed trichoscopy features of pemphigus lesions were: extravasations (18/19; 94.7%) and yellow hemorrhagic crusts (11/19; 57.9%). Yellow dots with whitish halo were observed in 6/19 (31.6%) patients with pemphigus. White polygonal structures were observed in pemphigus foliaceus (6/10; 60%), but not in pemphigus vulgaris. Vascular abnormalities were more frequent in pemphigus vulgaris, when compared to pemphigus foliaceus, and were associated with a severe course of disease. Linear serpentine vessels were the most frequent vascular abnormality in patients with pemphigus vulgaris and pemphigus foliaceus (77.8% and 30%, respectively). CONCLUSION: Trichoscopy may serve as a useful supplementary method in the differential diagnosis of pemphigus, especially in cases of desquamative or exudative lesions limited to the scalp. Extravasations, yellow hemorrhagic crusts, yellow dots with whitish halo, white polygonal structures and linear serpentine vessels are trichoscopy features which may suggest the diagnosis of pemphigus. .

Pénfigo foliáceo variedad seborreica: reporte de un caso / Pemphigus foliaceus seborrheic variety: a case report / Pénfigo foliáceo variedade seborreica: relato de caso

El pénfigo eritematoso o seborréico, también denominado síndrome de Senear-Usher es la variedad leve y localizada del pénfigo foliáceo, de baja incidencia. La mayor parte de los casos se han reportado en adultos entre la segunda y tercera década de la vida, promedio de 54 años, sin predominio entre razas o sexo. Su etiología se debe a la presencia de anticuerpos anti IgG contra la desmogleina 1 de los queratinocitos de la capa granulosa. Clínicamente se presenta en forma de placas eritematoescamosas o eritematocostrosas bien definidas, de aspecto y distribución seborreica (cara, cuello y tronco), que se exacerban a la exposición solar. Su diagnóstico clínico puede ser difícil, ya que se superpone clínicamente con el lupus eritematoso discoide y la dermatitis seborreica, por lo cual es importante tenerlo en cuenta como diagnóstico diferencial en lesiones infiltradas en dorso nasal y región malar en patrón de alas de mariposa. Se presenta el caso clínico de un paciente con pénfigo foliáceo variedad seborreica una entidad de baja incidencia.

Pemphigus erythematosus or seborrheic, also called Senear - Usher syndrome,is a mild, localized variety of pemphigus foliaceus, an entity of low incidence. Most cases have been reported in adults between second and third decades of life, average 54 years, no difference between race or sex. Etiology is due to the presence of IgG antibodies against desmoglein 1 in keratinocytes of the granular layer. Clinically, defined erythematous plaques, seborrheic distribution aspect (face, neck and trunk), which are exacerbated by sun exposure. Clinical diagnosis can be difficult as clinically overlaps with discoid lupus erythematosus and seborrheic dermatitis. So, it is important to be considered as differential diagnosis in infiltrated nasal lesions, dorsum and malar region butterfly pattern. We report a case of pemphigus foliaceus- seborrheic variety, a low incidence entity.

O pênfigo eritematoso do tipo seborréico, também chamada de síndrome Senear -Usher é variedade leve e localizada do pênfigo foliáceo , de baixa incidência , a maioria dos casos foram relatados em adultos entre a segunda e terceira década de vida , com idade media de 54 anos, sem predominância entre raças ou sexo. A sua etiologia é devido à presença de anticorpos anti - IgG de desmogleína 1 dos queratinócitos da camada granular . Clinicamente, apresenta-se como placas eritematosas ou eritematocostrosas bem definidos, de aspecto e distribuição seborreica (face, pescoço e tronco), que são agravadas pela exposição ao sol. Seu diagnóstico clínico pode ser difícil, pois se sobrepõe clinicamente com lúpus eritematoso discóide e dermatite seborreica, por isso é importante te-lo em mente como diagnóstico diferencial nas lesões infiltradas no dorso da nariz e região malar com asas de borboleta. Apresenta-se o caso de um paciente com pênfigo foliáceo do tipo seborreico uma entidade de baixa incidência com poucos casos relatados na literatura.

IgG/IgA pemphigus reactive with desmoglein 1 with additional undetermined reactivity with epidermal basement membrane zone.

IgG/IgA pemphigus is an extremely rare subset of pemphigus, showing anti-keratinocyte cell surface antibodies of both IgG and IgA classes. Herein, we describe a unique case of IgG/IgA pemphigus with clinical features of edematous erythema and peripheral vesiculopustules. Histopathology showed the presence of subcorneal pustules and acantholytic blisters in the mid-epidermis with neutrophilic infiltration and eosinophilic spongiosis. Direct immunofluorescence of perilesional skin showed both IgG and IgA deposits to keratinocyte cell surfaces and unusual granular deposits of IgG, IgM, and C3 along basement membrane zone. On enzyme linked immunosorbent assay , the auto-antibodies were found to be reactive to desmoglein 1 antigen. Various clinical, histopathological, and immunological findings in our case overlapped with the features of IgA pemphigus, pemphigus herpetiformis, and pemphigus foliaceus. These findings indicate that IgG/IgA pemphigus may be a transitional form between IgA pemphigus and pemphigus herpetiformis, and thus provides insight into the pathogenicity of this rare disorder.

Selective Elevation of Antibodies to Desmoglein 1 during the Transition from Mucocutaneous to Cutaneous Type Pemphigus Vulgaris

No abstract available.

Fogo selvagem: reporte de dos casos y revisión del tema / Fogo selvagem: report of two cases and review of literature

El fogo selvagem es un tipo de pénfigo foliáceo con características demográficas propias. Se presenta en niños y adolescentes y se caracteriza por la formación de ampollas subcórneas debido a la presencia de autoanticuerpos contra la desmogleína 1. Se presentan dos pacientes con este diagnóstico procedentes de la Amazonia colombiana.

Retinoid Induces the Degradation of Corneodesmosomes and Downregulation of Corneodesmosomal Cadherins: Implications on the Mechanism of Retinoid-induced Desquamation

BACKGROUND: Topical retinoids induce skin fragility. As corneodesmosomes are important adhesion structures in the epidermal cohesion, an effect of retinoids on corneodesmosomes has been suspected. OBJECTIVE: The aim of this study was to investigate the effect of retinoid on the expression of corneodesmosomal components including desmoglein (DSG) 1, desmocollin (DSC) 1, corneodesmosin (CDSN) and kallikrein (KLK)s. METHODS: 2% all-trans-retinol or ethanol was applied to the back of hairless mice for five days, and the structure of the stratum corneum was examined by transmission electron microscopy. The cultured human keratinocytes were treated with all-trans-retinoic acid (RA) in low or high calcium media for 24 hours. RESULTS: Topical retinol increased corneocyte detachment and degradation of corneodesmosomes. RA significantly decreased DSG1 and DSC1 expression at the mRNA and protein levels in keratinocytes that were cultured in both low- and high-calcium media. On the other hand, CDSN mRNA levels did not decrease in low-calcium media or increase in high-calcium media after RA treatment. KLK5 and KLK7 expression did not increase after RA treatment. CONCLUSION: Our results indicate that DSG1 and DSC1 downregulation by RA could be related to the increased degradation of corneodesmosomes and consequent desquamation induced by retinoids.

Analysis of the reactivity of indirect immunofluorescence in patients with pemphigus foliaceus and pemphigus vulgaris using rat bladder epithelium as a substrate

OBJECTIVES: To evaluate the reactivity of indirect immunofluorescence using rat bladder epithelium as a substrate in patients with pemphigus foliaceus and pemphigus vulgaris from the Department of Dermatology, University of São Paulo Medical School, Brazil. METHODS: Thirty-two patients (8 male and 24 female) from the Department of Dermatology, University of São Paulo Medical School, were selected. Three had mucosal pemphigus vulgaris, 20 had mucocutaneous pemphigus vulgaris, and 9 had pemphigus foliaceus. Patients’ sera were tested by indirect immunofluorescence performed on human foreskin and rat bladder epithelium and by ELISA assays utilizing baculovirus-expressed recombinant desmoglein 3 and desmoglein 1. RESULTS: No patients with mucosal pemphigus vulgaris, 5 of 20 patients with mucocutaneous pemphigus vulgaris (25 percent) and 4 of 9 patients with pemphigus foliaceus (44 percent) had positive indirect immunofluorescence using rat bladder epithelium as a substrate. CONCLUSION: Indirect immunofluorescence using rat bladder epithelium as a substrate is recommended whenever a diagnosis of paraneoplastic pemphigus is considered. The identification of a subset of pemphigus foliaceus and pemphigus vulgaris patients that recognizes desmoplakins by this laboratory tool is critical to avoid the misdiagnosis of paraneoplastic pemphigus.

Características epidemiológicas e inmunopatológicas de una cohorte de sujetos sanos positivos para anticuerpos anti desmogleína 1 procedentes de áreas endémicas de pénfigo foliáceo y vulgar del Perú / Epidemiological and immunopathologic characteristics in a cohort of healthy subjects for desmoglein 1 autoantibodies from endemic areas for endemic pemphigus foliaceus and vulgaris of Peru

OBJETIVO: Determinar las características epidemiológicas e inmunopatológicas de una cohorte de sujetos clínicamente sanos positivos para anticuerpos anti desmogleína 1 de Pueblo Libre y Nueva Requena (Ucayali), áreas endémicas de pénfigo foliáceo y vulgar del Perú. MATERIAL Y MÉTODOS: Estudio descriptivo, longitudinal y observacional. Los sujetos clínicamente sanos fueron evaluados por un dermatólogo para confirmarse la ausencia de enfermedades ampollares. Se obtuvo muestras de sangre para el estudio inmunopatológico mediante inmunofluorescencia indirecta (IFI), inmunoprecipitación (IP) y ELISA. Una vez detectados los sujetos positivos para anticuerpos anti desmogleína 1 se obtuvo datos epidemiológicos como edad, sexo, ocupación, exposición a insectos hematófagos, ingesta de alimentos con potencial acantolítico, exposición a mercurio, uso de cosméticos tradicionales y características de la vivienda; y fueron seguidos por un período de 4 años. RESULTADOS: Se captó a 21 sujetos clínicamente sanos positivos para anticuerpos anti desmogleína 1, el 52.4 por ciento correspondió al sexo femenino. Luego del seguimiento no se documentó el viraje a la fase clínica de pénfigo foliáceo endémico en ninguno de ellos. Las viviendas de los sujetos condicionaban la exposición a insectos hematófagos. El 9.5 por ciento presentó en la IFI anticuerpos contra los espacios intercelulares de los queratinocitos. La IP anti desmogleína 1 fue levemente positiva en el 61.9 por ciento y francamente positiva en el 4.8 por ciento. El ELISA para anticuerpos IgG anti desmogleína 1 fue positivo en el 100 por ciento de los sujetos predominando las subclases IgG1 e IgG2 (71.4 por ciento cada una). El ELISA para anticuerpos IgM anti desmogleína 1 fue positivo en el 19.0 por ciento. Para los anticuerpos anti desmogleína 3, la IP fue negativa en todos los casos mientras que el ELISA fue positivo en el 81.0 por cientoCONCLUSIONES: Una fracción de sujetos de áreas endémicas.

AIM: To determine epidemiologic and immunopathologic characteristics in a cohort of healthy subjects who were positive for antidesmoglein 1 antibodies in Pueblo Libre and Nueva Requena(Ucayali), endemic areas for endemic pemphigus foliaceus and vulgaris of Peru. MATERIAL AND METHODS: Descriptive, longitudinal and observational study. The healthy subjects were examined by a dermatologist to confirm that there were no blistering diseases. A blood sample was drawn for immunopathologic studies: indirect imunofluorescence (IFI), immunoprecipitation (IP) and ELISA. In patients who had positive results, epidemiologic data was obtained: age, sex, ocupation, exposure to haematophagus insects, ingestion of food with achantolytic properties, mercury exposure, use of tradicional cosmetics and house characteristics. Subjects were followed for a 4 year period. RESULTS: We enrolled 21 healthy subjects positive for desmoglein 1 autoantibodies who were after the 4 years follow-up period, none of the subjects went into the clinical active phase of pemphigus. The houses of these subjects conditioned the presence of haematophagus insects. 9.5 per cent was positive by IFI, 61.9 per cent was sligthly positive by IP and 4.8 per cent strongly positive. 100 per cent of subjects were positive for anti desmoglein 1 antibodies, being 71.4 per cent positive for IgG1 and IgG2 as well. ELISA for IgM antidesmoglein 1 antibodies was positive in 19 per cent of the subjects. Regarding antidesmoglein 3 antibodies none by IP and 81 per cent was positive by ELISA. CONCLUSIONS: A healthy subset of patients from endemic areas for endemic pemhigus foliaceus and vulgaris had anti desmoglein 1 and 3 antibodies, most likely due to environmental factors but none of them went into the clinical active phase of pemphigus in a 4 year follow-up period.

Desmoglein ELISA in the diagnosis of pemphigus and its correlation with the severity of pemphigus vulgaris

Anti-desmoglein 3 and 1 autoantibodies are involved in the pathogenesis of pemphigus diseases. Our objective was to assess the value of ELISA in the diagnosis of pemphigus and its correlation with the severity of pemphigus vulgaris. Based on clinical presentation and histopathologic confirmation for the diagnosis of the pemphigus, 38 patients took part in the study. Sera of the patients were tested by desmoglein 1 and desmoglein 3 ELISA. Also, direct immunofluorescence was performed for all patients which revealed positive results in 36 patients [94.7%]. ELISA was positive in 37 of 38 pemphigus patients [Sensitivity: 97.3%]. The relationship between desmoglein 1 index values and skin severity was statistically significant [p<0.05]. Desmoglein 3 index values increased with oral severity although this was not statistically significant. Iranian patients similar to Indian patients had higher positive anti-desmoglein 1 autoantibodies. Desmoglein-ELISA test is appropriate in the diagnosis of pemphigus. Desmoglein 1 index value is statistically correlated with the severity of pemphigus vulgaris

Evaluation of sensitivity and specificity of enzyme-linked immunosorbent assay (ELISA) for detecting antidesmoglein 1 and 3 in Thai patients with pemphigus vulgaris and foliaceus.

OBJECTIVE: Pemphigus is an acquired autoimmune blistering skin diseases, of which pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two major subtypes. A novel commercial enzyme-linked immunosorbent assay (ELISA) against Dsg1 and Dsg3 has been well established for diagnosis and prediction of disease activity in PF and PV. At present, the benefit of anti-Dsg 1 and anti-Dsg 3 IgG by ELISA in the diagnosis of pemphigus in Thai patients has never been reported. The objective of the present study is to evaluate the sensitivity and specificity of ELISA for detecting antidesmoglein 1 and 3 in Thai patients with pemphigus. MATERIAL AND METHOD: Retrospective review of anti-Dsg1 and anti-Dsg3 antibody ELISA test results from 48 serum samples collected from 27 patients with PV seven patients with PF and 14 controls. RESULTS: The sensitivity of Dsg1 and Dsg3 ELISA for all patients with PV was 64% and 77.8% respectively. When subgrouped into only PV patients with new diagnosis, the sensitivity of Dsg 1 and Dsg 3 ELISA increased to 85.7% and 100%. In all PF patients, the sensitivity of anti-Dsg 1 ELISA was 71.4% and 100% for newly diagnosed PF cases. Anti-Dsg 3 was not detected in the PF group. The specificity of ELISA for anti-Dsg 1 and anti-Dsg 3 in both types of pemphigus was 85.7% and 92.3% respectively. CONCLUSIONS: Dsg 1 and Dsg 3 ELISA is a simple, highly sensitive and specific test in Thai pemphigus patients with 100% sensitivity in the diagnosis of both new pemphigus vulgaris and foliaceus patients.

The Expressions of Desmoglein 1 and 3 according to Chronologic Skin Aging / 대한피부과학회지

BACKGROUND: Desmogleins are transmembrane glycoproteins of the desmosome which provide mechanical strength to epithelial tissue. Desmogleins have so far, been implicated in several diseases such as pemphigus, striate palmoplantar keratoderma, 4S and squamous cell carcinomas. Skin cancer usually occurs in old age. And there are reports that the expression of desmogleins are increased in squamous cell carcinoma. However the role of desmogleins in skin aging has not yet been reported. OBJECTIVE: The purpose of this study was to investigate the expression of desmoglein 1 and 3 according to chronologic skin aging. METHODS: A total of 6 normal tissue samples from sun-protected skin of different age groups (from 34-year-old to an 84-year-old) and 1 squamous cell carcinoma tissue from a 72-year-old patient were taken. Western blotting and immunohistochemical staining were performed with anti desmoglein 1 and 3 antibodies. The expression of desmoglein 1 and 3 by Western blotting were calculated semiquantitatively by a densitometer. RESULTS: The expression of desmoglein 1 was 0.382 in the 34-year-old, 0.450 in the 45-year-old, 0.369 in the 56-year-old, 0.761 in the 65-year-old, 1.035 in the 77-year-old and 1.329 ODu/mm2 in the 84-year-old. The expression of desmoglein 3 was 0.830 in the 34-year-old, 0.984 in the 45-year-old, 1.029 in the 56-year-old, 1.534 in the 65-year-old, 1.714 in the 77-year-old and 1.878 ODu/mm2 in the 84-year-old. In immunohistochemical staining, the expression of Dsg1 increased from the basal layer to the granular layer and Dsg3 was expressed in the basal and suprabasal layers. CONCLUSION: The expression of desmoglein 1 and 3 were increased according to chronologic skin aging.

Study of desmoglein 1 and 3 antibody levels in relation to disease severity in Indian patients with pemphigus.

OBJECTIVES: To conduct a cross-sectional study to compare Dsg1 and Dsg3 antibody levels independently with severity of disease activity in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). METHODS: Blood samples from 44 patients with pemphigus (PV-38, PF-6) were analyzed using ELISA. The severity of skin and mucosal disease was graded using a score from 0 to 3. RESULTS: A statistically significant correlation between increase in Dsg 3 antibody titres with severity of oral involvement and Dsg 1 titres with severity of skin involvement was found in both PV and PF patients (p < 0.01). However, we were unable to demonstrate a relationship between increased titres of Dsg1 and Dsg 3 antibodies with oral and skin involvement respectively. CONCLUSION: This study suggests that the severity of skin and oral disease in pemphigus is determined by the quantities of Dsg1 and Dsg3 antibodies respectively.

Mechanism of alopecia in patients with paraneoplastic pemphigus / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the relationship between the levels of antidesmoglein (DSG) 1, 3 antibodies in the sera of patients with paraneoplastic pemphigus (PNP) and alopecia.</p><p><b>METHODS</b>Sera from PNP patients, bullous pemphigoid patients, and normal healthy subjects were collected and 2 tissue samples from 2 healthy scalps were resected. Anti-DSG 1, 3 antibodies in the sera of PNP patients were detected by enzyme-linked immunosorbent assay (ELISA). Indirect immunofluorescent assay was used to detect whether the antibodies in the sera of PNP patients binds with the follicular epithelium of normal healthy scalp.</p><p><b>RESULTS</b>Anti-DSG3 autoantibody was strongly positive and anti-DSG1 weakly positive in one patient, while both two antibodies were negative in the other patient. Their sera could bind to keratinocytes and follicular epithelium in human scalp. Immunofluorescent signals were found on the intercellular epidermal cell surface and outer root sheath of the follicular epithelium. However, the immunofluorescent signals in the section incubating with serum of bullous pemphigoid were only found on basal membrane zone. No signals were found in the section incubating with normal healthy serum.</p><p><b>CONCLUSION</b>Alopecia in PNP patients are correlated with the anti-DSG3.</p>

Analysis of HPV-16 E6-related gene expression using cDNA microarray / 대한산부인과학회잡지

OBJECTIVE: To examine the effect of HPV-16 E6 expression on the transcription of cellular genes, we used cDNA microarray in HPV-16 E6 transfected stable cancer cell lines. METHODS: Using cDNA microarray consisting of 1,024 genes, we have performed a systematic characterization of gene expression in A549E6 human lung adenocarcinoma and RC10.1 human colon adenocarcinoma cell lines stably expressing HPV-16 E6 gene. The up-regulated and down-regulated genes were classified into the different functional categories; oncogenes, apoptosis, cell cycle, signal transduction, gene regulation, immune response, cell adhesion, protein transport, metabolism, redox control and angiogenesis. RESULTS: Among 1,024 known genes and ESTs (expressed sequence tags) tested, we found 27 up- regulated and 43 down-regulated genes in A549E6 (HPV-16 E6) compared to A549. The major up-regulated genes were as follows. GTPase-activating protein Rho 4, transcription factor D2, IKAROS, integrin-alpha 6, cadherin 11, ephrin-beta 2, RAN binding protein 2, branched-chain amino transferase 2. The major down-regulated genes were as follows. K-ras 2, CDC (cell division cycle) 37, CDC16, CDC7L1, IRF3, interferon-gamma-inducible protein 30, cadherin 6, desmoglein 1, desmocollin 2, endothelin 2. Also, we found 48 up-regulated and 34 down-regulated genes in RC10.1 (HPV-16 E6) compared to RKO. The major up-regulated genes were as follows. Colon cancer familial nonpolyposis type 1 (COCA 1), Bcl 2, jagged 1, MAP2K6, E2F1, ephrin receptor-beta 2, ephrin-beta 2, desmoglein 1, transforming growth factor-beta 3. The major down-regulated genes were as follows. KIT, Rad51C, Bcl 2 antagonist killer 1, STAT 4, epidermal growth factor receptor, high mobility group protein 2, cadherin 11, cadherin 12, cadherin 3, integrin-alpha 1, intergrin-alpha 8, chromosome segregation 1-like. CONCLUSION: Various expression patterns of cellular genes by HPV-16 E6 could be wholy grasped and classified into different functional groups using both cell line system stably expressed HPV-16 E6 and cDNA microarray analysis. These analysis methods must be helpful to understand multiple effects of a specific gene on cellular genes in a short period.

Detection of pemphigus antigens by immunoblot analysis and indirect immunofluorescence using cultured keratinocytes / 대한피부과학회지

BACKGROUND: Pemphigus are chronic autoimmune blistering disorcers characterized by acantholysis. In addition to pemphigus vulgaris(PV), the major clinical variarts are pemphigus foliaceus(PF), paraneoplastic pemphigus(PNP) and drug-induced pemphigus(DP). Detection of pemphigus antigen is important for differential diagnosis as well as research work. Most investigators have identified pemphigus antigens by means of immunoprecipitation using metabolically radiolabeled cultured keratinocytes. However, immunorepitation is generally more expensive, hazardous and time-consuming than immunoblotting. Therefore, establishment of the immunoblotting as a standard technique for the detection of the pemphig us antigens is desirable. OBJECTIVE: To characterized pemphigus antigens by an immunobloting analysis of human epidermal extract and by indirect itnmunofluroscence study using human of cultured keratinocytes as a substraie. METHOD: We performed imrnunoblotting analysis af sera from patieiits with PV, PF, PNP and DP with human epidermal extract as a source of antigen. Indirect immunof uorescence study was also performed using human keratinocytes cultured in high or low calcium media for detection of pemphigus antigens. RESULTS: In an immunoblotting analysis, all(9/9) PV sera showed secific reactivities with a 130-KD protein and all(5/5) FF sera showed reactivities with a 150-KK protein, which is most likely desmoglein 1. Furthermore, one of nine PV serum also reacted with a 150-KD protein, which seems to be the identical antigen detected in PF. All PNP(3/3) sera showed reactivities with two protein bands, 210KD and 190KD. In our indirect imrnunofluorescence study using culltured human keratinocytes as a substrate, when keratinocytes were grown in low calcium media, no pimphigus antigens could be detected. However, when grown in high calciurn media, pemphigus vulga ris and paraneoplastic pernphigus antigens were present t the cell-cell contact areas with a puncta;e pattern, whereas pemphigus foliaceus antigen was not, presint in keratinocytes even when cultured in high calcium media. CONCLUSION: Our results suggests (1) immunoblotting analysis is a reliable technique for defining pemphigus antigen and could be a valuable tool for the differentiation of PV, PF and PNP and(2) PF antigen rnay not be expresseden cultured keratinocytes.