RESUMO
Bullous pemphigoid (BP) is a cutaneous autoimmune blistering disorder. Recently, it has been reported that dipeptidyl peptidase-4 inhibitors (DPP4i) is associated with the development of BP (DPP4i-BP). Patients with DPP4i-BP have autoantibodies (autoAbs) preferentially targeting full-length BP180, but not the BP180NC16a domain. In this report, we described a case of anti-BP230 antibody (Ab)-positive BP receiving DPP4i. A 78-year-old male with a medical history of type 2 diabetes receiving vildagliptin at 100 mg daily for 38 months was referred to our hospital with itching blisters on his body and extremities. Skin biopsy showed subepidermal bulla with eosinophil infiltration. Direct immunofluorescence staining revealed a linear staining pattern with complement C3 and IgG at the subepidermal basement membrane zone. By laboratory testing, autoAbs against BP180NC16a and full-length BP180 were negative by enzyme-linked immunosorbent assay (ELISA); however, anti-BP230 Abs were positive by ELISA (index: 123.91). His HLA genotype was DQB1*04:01 and 05:01. Based on these results, we diagnosed the patient with anti-BP230 Abs-positive BP associated with DPP4i. To the best of our knowledge, this is the first case of DPP4i-BP with only anti-BP230 Abs. Further accumulation of DPP4i-BP cases is needed to clarify the relationship between overall features of DPP4i-BP and anti-BP230 Abs.
Assuntos
Autoanticorpos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Distonina/imunologia , Penfigoide Bolhoso/etiologia , Penfigoide Bolhoso/imunologia , Vildagliptina/efeitos adversos , Idoso , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Humanos , Masculino , Fatores de Tempo , Vildagliptina/administração & dosagem , Vildagliptina/uso terapêuticoRESUMO
BACKGROUND: Autoimmune blistering diseases (AIBDs) are a group of fatal diseases with specific autoantibodies. BIOCHIP mosaic is a novel and all-in-one measure used for the rapid diagnosis of AIBDs. OBJECTIVES: To evaluate the diagnostic accuracy based on BIOCHIP mosaic (FA1501-1005-60) in Chinese patients with AIBDs. MATERIALS AND METHODS: Seventy-seven patients with AIBDs and 20 controls were enrolled. The BIOCHIP mosaic was performed using both serum and plasma samples. RESULTS: Based on BIOCHIP mosaic, the data from paired plasma and serum samples demonstrated a high degree of concordance (Cohen's kappa = 0.896-1.000) for autoantibodies against Dsg1, Dsg3, BP180-NC16A-4X, BP230gC, prickle-cell desmosomes, and pemphigoid antigens. Moreover, BIOCHIP mosaic also demonstrated a high degree of consistency for the detection rate of anti-Dsg1, Dsg3, plakins, BP180-NC16A-4X and non-collagenous domain of type VII collagen autoantibodies for the diagnosis of pemphigus foliaceus (77.3%), pemphigus vulgaris (88.6%), paraneoplastic pemphigus (100.0%), bullous pemphigoid (92.8%) and epidermolysis bullosa acquisita (99.0%), respectively. CONCLUSION: Using BIOCHIP mosaic, serum and plasma samples may be used interchangeably at 1/10 dilution. Overall, the BIOCHIP mosaic was shown to be a useful and accurate tool for the diagnosis of AIBDs.
Assuntos
Doenças Autoimunes/diagnóstico , Técnica Indireta de Fluorescência para Anticorpo/métodos , Dermatopatias Vesiculobolhosas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Autoanticorpos/sangue , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Estudos de Casos e Controles , Desmogleína 1/imunologia , Desmogleína 3/imunologia , Distonina/imunologia , Humanos , Proteínas com Domínio LIM/imunologia , Pessoa de Meia-Idade , Colágenos não Fibrilares/imunologia , Plaquinas/imunologia , Valor Preditivo dos Testes , Dermatopatias Vesiculobolhosas/imunologia , Proteínas Supressoras de Tumor/imunologia , Adulto Jovem , Colágeno Tipo XVIIAssuntos
Autoanticorpos/sangue , Transtornos de Deglutição/diagnóstico , Esôfago/patologia , Penfigoide Mucomembranoso Benigno/diagnóstico , Autoanticorpos/imunologia , Autoantígenos/imunologia , Biomarcadores/sangue , Biópsia/estatística & dados numéricos , Transtornos de Deglutição/sangue , Transtornos de Deglutição/etiologia , Diagnóstico Tardio/estatística & dados numéricos , Distonina/imunologia , Endoscopia do Sistema Digestório/estatística & dados numéricos , Esôfago/diagnóstico por imagem , Esôfago/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Colágenos não Fibrilares/imunologia , Penfigoide Mucomembranoso Benigno/sangue , Penfigoide Mucomembranoso Benigno/complicações , Encaminhamento e Consulta/estatística & dados numéricos , Colágeno Tipo XVIIRESUMO
Bullous pemphigoid (BP) is a common autoimmune blistering disease in which autoantibodies target the hemidesmosomal components BP180 and/or BP230 in basal keratinocytes. In BP, 80 to 90% of autoantibodies target the juxtamembranous extracellular non-collagenous 16th A (NC16A) domain of BP180. Recently, the administration of dipeptidyl peptidase-IV inhibitors (DPP4i), which are widely used as antihyperglycemic drugs, has been recognized to be a causative factor for BP. DPP4i-associated BP (DPP4i-BP) autoantibodies tend to target epitopes on non-NC16A regions of BP180, and the pathomechanism for the development of the unique autoantibodies remains unknown. To address the characteristics of DPP4i-BP autoantibodies in detail, we performed epitope analysis of 18 DPP4i-BP autoantibodies targeting the non-NC16A domains of BP180 using various domain-specific as well as plasmin-digested polypeptides derived from recombinant BP180. Firstly, Western blotting showed that only one DPP4i-BP serum reacted with the epitopes on the intracellular domain of BP180, and no sera reacted with the C-terminal domain of the molecule. In addition, only 2 DPP4i-BP sera reacted with BP230 as determined by enzyme-linked immunosorbent assay. Thus, DPP4i-BP autoantibodies were found to mainly target the non-NC16A mid-portion of the extracellular domain of BP. Interestingly, Western blotting using plasmin-digested BP180 as a substrate revealed that all of the DPP4i-BP sera reacted more intensively with the 97-kDa processed extracellular domain of BP180, which is known as the LABD97 autoantigen, than full-length BP180 did. All of the DPP4i-BP autoantibodies targeting the LABD97 autoantigen were IgG1, and IgG4 was observed to react with the molecule in only 7 cases (38.9%). In summary, the present study suggests that IgG1-class autoantibodies targeting epitopes on the processed extracellular domain of BP180, i.e., LABD97, are the major autoantibodies in DPP4i-BP.
Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Epitopos/imunologia , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Especificidade de Anticorpos , Autoantígenos/química , Autoantígenos/efeitos dos fármacos , Western Blotting , Dipeptidil Peptidase 4/imunologia , Inibidores da Dipeptidil Peptidase IV/imunologia , Distonina/química , Distonina/imunologia , Ensaio de Imunoadsorção Enzimática , Epitopos/química , Feminino , Fibrinolisina/farmacologia , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Colágenos não Fibrilares/química , Colágenos não Fibrilares/efeitos dos fármacos , Penfigoide Bolhoso/imunologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Domínios Proteicos/imunologia , Proteínas Recombinantes/efeitos dos fármacos , Proteínas Recombinantes/imunologia , Colágeno Tipo XVIIAssuntos
Autoanticorpos/sangue , Laminina/imunologia , Penfigoide Bolhoso/imunologia , Sarcoptes scabiei/imunologia , Escabiose/imunologia , Adulto , Animais , Antiparasitários/administração & dosagem , Autoanticorpos/imunologia , Autoantígenos/imunologia , Biópsia , Distonina/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Ivermectina/administração & dosagem , Masculino , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/parasitologia , Escabiose/tratamento farmacológico , Escabiose/parasitologia , Testes Sorológicos , Pele/imunologia , Pele/parasitologia , Pele/patologia , Resultado do Tratamento , Colágeno Tipo XVIIAssuntos
Penfigoide Bolhoso/diagnóstico , Pele/patologia , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoantígenos/imunologia , Biópsia , Distonina/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/patologia , Colágeno Tipo XVIIRESUMO
The clinical features of bullous pemphigoid are extremely polymorphous. Several atypical forms of bullous pemphigoid have been described, and the diagnosis critically relies on immunopathological findings. We describe three bullous pemphigoid patients characterized by palmoplantar keratoderma, diffused hyperkeratotic cutaneous lesions and extremely high levels of immunoglobulin E serum. The diagnosis of bullous pemphigoid should be taken into account in patients presenting diffused hyperkeratotic cutaneous lesions and palmoplantar keratoderma, even in the absence of blisters. Alteration of the keratinization process, that could occur in patients with genetic mutations in desmosomal and hemidesmosomal genes, may also be due to circulating autoantibodies against hemidesmosomal proteins in these bullous pemphigoid patients.
Assuntos
Autoanticorpos/sangue , Imunoglobulina E/sangue , Ceratodermia Palmar e Plantar/patologia , Penfigoide Bolhoso/patologia , Adulto , Idoso , Autoantígenos/imunologia , Produtos Biológicos/uso terapêutico , Biópsia , Distonina/imunologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Ceratodermia Palmar e Plantar/sangue , Ceratodermia Palmar e Plantar/tratamento farmacológico , Ceratodermia Palmar e Plantar/imunologia , Masculino , Pessoa de Meia-Idade , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/sangue , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/imunologia , Pele/imunologia , Pele/patologia , Colágeno Tipo XVIIRESUMO
There is currently a growing interest in new diagnostic tools of the oral cavity and mucosa which are non-invasive, repeatable and reliable. A diagnosis of a suspected, autoimmune pathology was made regarding a 57-year-old patient with desquamative gingivitis. However, a negative Nikolsky's sign did not seem to indicate a diagnosis of mucous membrane pemphigoid neither was there any indication as to the optimum location for an incisional biopsy. As an imaging method, the use of optical coherence tomography (OCT) has enabled the obtaining of tomographic (cross-sectional) scans of tissue. Such images are acquired prior to and after verifying Nikolsky's sign, thereby enabling the clinician to identify the presence (or not) of subepithelial bullae. Thereafter, an assessment of changes in the subepithelium (the split) can be performed, even in the absence of a suitable clinical picture, such as, for example, a negative Nikolsky's sign. Histological analysis and the use of indirect immunofluorescence have facilitated a diagnosis of mucous membrane pemphigoid, an autoimmune pathology, which can be confirmed with the appearance of subepithelial bullae. OCT was found to be a valid, non-invasive, auxiliary diagnostic device, capable of revealing in vivo and real-time bullae, which were hitherto clinically undetectable.
Assuntos
Gengivite/diagnóstico , Mucosa Bucal/diagnóstico por imagem , Penfigoide Mucomembranoso Benigno/diagnóstico , Tomografia de Coerência Óptica/métodos , Administração Tópica , Autoanticorpos/análise , Autoanticorpos/imunologia , Clobetasol/uso terapêutico , Distonina/imunologia , Epitélio/diagnóstico por imagem , Epitélio/imunologia , Epitélio/patologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Gengivite/tratamento farmacológico , Gengivite/imunologia , Gengivite/patologia , Glucocorticoides/uso terapêutico , Humanos , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Penfigoide Mucomembranoso Benigno/imunologia , Penfigoide Mucomembranoso Benigno/patologiaAssuntos
Autoanticorpos/imunologia , Imunoglobulina G/imunologia , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/imunologia , Prednisolona/uso terapêutico , Idoso , Autoantígenos/imunologia , Biópsia por Agulha , Distonina/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Immunoblotting/métodos , Imuno-Histoquímica , Masculino , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/patologia , Resultado do Tratamento , Colágeno Tipo XVIIAssuntos
Fatores Imunológicos/uso terapêutico , Omalizumab/uso terapêutico , Penfigoide Bolhoso/tratamento farmacológico , Pele/efeitos dos fármacos , Idoso , Autoanticorpos/sangue , Autoantígenos/imunologia , Biomarcadores/sangue , Biópsia , Distonina/imunologia , Feminino , Imunofluorescência , Humanos , Imunoglobulina E/sangue , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/sangue , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/imunologia , Indução de Remissão , Índice de Gravidade de Doença , Pele/imunologia , Pele/patologia , Resultado do Tratamento , Colágeno Tipo XVIIRESUMO
The dermal-epidermal junction consists of a network of several interacting structural proteins that strengthen adhesion and mediate signalling events. This structural network consists of hemidesmosomal-anchoring filament complexes connecting the basal keratinocytes to the basement membrane. The anchoring filaments in turn interact with the anchoring fibrils to attach the basement membrane to the underlying dermis. Several of these structural proteins are recognized by autoantibodies in pemphigoid diseases, a heterogeneous group of clinically and immunopathologically diverse entities. Targeted proteins include the two intracellular plakins, plectin isoform 1a and BP230 (also called bullous pemphigoid antigen (BPAG) 1 isoform e (BPAG1e)). Plectin 1a and BP230 are connected to the intermediate filaments and to the cell surface receptor α6ß4 integrin, which in turn is connected to laminin 332, a component of the anchoring filaments. Further essential adhesion proteins are BP180, a transmembrane protein, laminin γ1 and type VII collagen. Latter protein is the major constituent of the anchoring fibrils. Mutations in the corresponding genes of these adhesion molecules lead to inherited epidermolysis bullosa emphasizing the importance of these proteins for the integrity of the dermal-epidermal junction. This review will provide an overview on the structure and function of the proteins situated in the dermal-epidermal junction targeted by autoantibodies.