RESUMO
Keratins are the major amyloid fibril component in localized cutaneous amyloidosis. We analyzed the amyloid components in the skin of patients with localized cutaneous amyloidosis by immunohistochemical staining using antisera against extracellular matrix proteins and keratin 5 (K5). Fibulin-4 and K5 colocalized in the amyloid deposits. Using 14 synthetic peptides, we screened for amyloidogenic sequences in the C-terminal region of K5, including the α-helical rod domain and the tail domain. Two peptides stained with thioflavin T possessed a ß-sheet structure and formed amyloid-like fibrils. Among the amyloidogenic peptides, a peptide KT5-6 (YQELMNTKLALDVEIATYRKLLEGE) derived from the α-helical rod domain of K5 specifically bound to fibulin-4. In addition, amyloid formation of KT5-6 was accelerated by fibulin-4. These results suggest that degraded fragments of K5 containing the KT5-6 sequence form amyloid fibrils with fibulin-4. The data further suggest that degraded fragments of K5 and fibulin-4 have the potential to initiate cutaneous amyloidosis.
Assuntos
Doença Relacionada a Imunoglobulina G4/diagnóstico , Úlcera da Perna/etiologia , Úlcera Cutânea/etiologia , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Idoso , Feminino , Humanos , Doença Relacionada a Imunoglobulina G4/patologia , Úlcera da Perna/tratamento farmacológico , Úlcera da Perna/patologia , Pomadas , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/patologiaAssuntos
Diabetes Mellitus/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Cadeias beta de HLA-DQ/imunologia , Penfigoide Bolhoso/induzido quimicamente , Piperidinas/efeitos adversos , Uracila/análogos & derivados , Idoso , Feminino , Humanos , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/imunologia , Uracila/efeitos adversosRESUMO
Several sporadic cases, in which direct and indirect immunofluorescence studies simultaneously detected IgG and IgA autoantibodies to keratinocyte cell surfaces, have been reported mainly under the name of IgG/IgA pemphigus. However, there have been no systematic studies for this condition. In this study, we collected 30 cases of this condition from our cohort of more than 5,000 autoimmune bullous disease cases, which were consulted for our diagnostic methods from other institutes, and summarized their clinical and immunological findings. Clinically, there was no male-female prevalence, mean age of disease onset was 55.6 years, and mean duration before this condition was suspected was 18 months. The patients showed clinically bullous and pustular skin lesions preferentially on the trunk and extremities, and histopathologically intraepidermal pustules and blisters with infiltration of neutrophils and eosinophils. Immunologically, ELISAs frequently detected IgG and IgA autoantibodies to both desmogleins and desmocollins. From the characteristic clinical, histopathological, and immunological features, which are considerably different from those in classical IgG types of pemphigus, we propose this disease as a new disease entity with preferential name of intercellular IgG/IgA dermatosis (IGAD). This was the largest study of IGAD to date.
Assuntos
Autoanticorpos/imunologia , Dermatose Linear Bolhosa por IgA/classificação , Dermatose Linear Bolhosa por IgA/imunologia , Idoso , Idoso de 80 Anos ou mais , Desmocolinas/imunologia , Desmogleínas/imunologia , Feminino , Humanos , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Queratinócitos/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Pele/imunologia , Pele/patologiaRESUMO
BACKGROUND: Cochineal dye is used worldwide as a red coloring in foods, drinks, cosmetics, quasi-drugs, and drugs. The main component of the red color is carminic acid (CA). Carmine is an aluminum- or calcium-chelated product of CA. CA and carmine usually contain contaminating proteins, including a 38-kDa protein thought to be the primary allergen. Severe allergic reactions manifest as anaphylaxis. The aim of this study was to review all Japanese reported cases and propose useful diagnostic chart. METHODS: All reported Japanese cases of cochineal dye-induced immediate allergy were reviewed, and newly registered cases were examined by skin prick test (SPT) with cochineal extract (CE) and measurement of CE and carmine-specific serum IgE test. Two-dimensional (2D) western blotting using patient serum was conducted to identify the antigen. RESULTS: Twenty-two Japanese cases have been reported. SPT and the level of specific IgE test indicated that six cases should be newly registered as cochineal dye allergy. All cases were adult females, and all cases except three involved anaphylaxis; 13 cases involved past history of local symptoms associated with cosmetics use. Japanese strawberry juice and fish-meat sausage, and European processed foods (especially macarons made in France) and drinks were recent major sources of allergen. 2D western blotting showed that patient IgE reacted to the 38-kDa protein and other proteins. Serum from healthy controls also weakly reacted with these proteins. CONCLUSIONS: SPT with CE and determination of the level of CE and carmine-specific IgE test are useful methods for the diagnosis of cochineal dye allergy.
Assuntos
Alérgenos/efeitos adversos , Carmim/efeitos adversos , Corantes/efeitos adversos , Hipersensibilidade Imediata/induzido quimicamente , Hipersensibilidade Imediata/diagnóstico , Adulto , Povo Asiático , Feminino , Humanos , Hipersensibilidade Imediata/sangue , Hipersensibilidade Imediata/imunologia , Imunoglobulina E/sangue , Japão , Pessoa de Meia-Idade , Testes CutâneosAssuntos
Dermatite Atópica/genética , Ictiose Bolhosa de Siemens/genética , Proteínas de Filamentos Intermediários/genética , Queratina-2/genética , Adolescente , Adulto , Dermatite Atópica/complicações , Proteínas Filagrinas , Humanos , Ictiose Bolhosa de Siemens/complicações , Imunoglobulina E/sangue , Lactente , Recém-Nascido , MasculinoAssuntos
Terapia por Acupuntura/efeitos adversos , Argiria/etiologia , Migração de Corpo Estranho/diagnóstico por imagem , Ventrículos do Coração , Agulhas/efeitos adversos , Terapia por Acupuntura/instrumentação , Terapia por Acupuntura/métodos , Idoso , Evolução Fatal , Feminino , Migração de Corpo Estranho/complicações , Humanos , Espectrometria por Raios X/métodosAssuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Antígeno CTLA-4/genética , Diabetes Mellitus Tipo 1/induzido quimicamente , Antígenos HLA/genética , Pâncreas/patologia , Diabetes Mellitus Tipo 1/genética , Feminino , Humanos , Melanoma/tratamento farmacológico , Melanoma/secundário , Pessoa de Meia-Idade , Nivolumabe , Tamanho do Órgão/genética , Polimorfismo Genético , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
Importance: We found CARD14 mutations (2 de novo novel mutations and another previously reported mutation) in 3 of 3 patients with pityriasis rubra pilaris (PRP) type V, but not in patients with PRP of other types. Our findings, combined with the published literature, suggest that type V PRP, both familial and sporadic, can be caused by CARD14 mutations. Detailed clinical observation revealed that all 3 patients displayed unique patchy macular brown hyperpigmentation. Objective: To further determine how often patients with PRP have pathogenic mutations in CARD14 and to elucidate which clinical subtype of PRP is caused by CARD14 mutations. Design, Setting, and Participants: We sequenced the entire coding regions of CARD14 in genomic DNA from patients with 5 clinical subtypes of PRP. The detailed clinical features were analyzed in all the patients. The pathogenicity of each mutation was evaluated by several computational predictions. PRP was classified into 6 subgroups, types I to VI, based on clinical criteria. We categorized all the patients with PRP into the clinical subtypes using the classic PRP classification; 22 cases of PRP with varying subtypes were studied. Main Outcomes and Measures: The prevalence of CARD14 mutations in each subtype of PRP was evaluated. Clinical features and characteristics of patients with PRP with CARD14 mutations were analyzed. Results: Overall 22 patients with PRP were included in our study (12 men, 10 women; mean [SD] age, 26 [18] years). Among 3 patients with PRP type V, all were found to have CARD14 mutations: 2 de novo novel mutations (p.Cys127Ser and p.Gln136Leu), and another previously reported mutation (p.Gly117Ser). All were close to the reported pathogenic domains. In silico analysis of all 3 mutations suggested that they are functionally relevant to pathogenesis. All 3 patients displayed unique patchy macular brown hyperpigmentation additionally to other typical features of PRP. Patients with PRP type I and type IV, 1 patient each, had the rare variants in CARD14. Conclusions and Relevance: Pityriasis rubra pilaris type V is a distinct variant of PRP that is caused by CARD14 mutations. In addition, a rare variant of CARD14 might also be implicated in the pathophysiology of other forms of PRP.
Assuntos
Proteínas Adaptadoras de Sinalização CARD/genética , Guanilato Ciclase/genética , Proteínas de Membrana/genética , Pitiríase Rubra Pilar/classificação , Pitiríase Rubra Pilar/genética , Adolescente , Adulto , Criança , Feminino , Humanos , Inflamação/genética , Masculino , Mutação , Pitiríase Rubra Pilar/patologia , Adulto JovemRESUMO
Beneficial effects of Wy14643, an agonist for peroxisome proliferator-activated receptor (PPAR)α, on permeability barrier homeostasis-related functions of keratinocytes such as up-regulation of epidermal differentiation-related molecules and lipid synthesis, have been demonstrated. The present study demonstrated that Wy14643 reduced the expression of thymus and activation-related chemokine (TARC) and regulated on activation normal T cell expressed (RANTES) in both single- and 3D-cultured human keratinocytes. The combined data of the present and previous studies support the notion that Wy14643 could be a therapeutic agent that might simultaneously and directly modulate permeability barrier dysfunction and allergic inflammation in the pathogenesis of atopic dermatitis. As for the anti-microbial barrier function, the present study demonstrated that Wy14643 up-regulated expression of the anti-microbial peptide, human ß defensin 3, in cultured human keratinocytes only in mRNA levels but not in protein ones, suggesting that Wy14643 might not directly account for the up-regulation of the anti-microbial peptide which has been reported in vivo.