RESUMO
BACKGROUND: Pemphigus is an autoimmune disease characterized by the formation of intra-epidermal blisters. Patients develop auto-antibodies against desmoglein 1 and 3 proteins and induce acantholysis. OBJECTIVE: This work addresses the issue of whether the Fas pathway mediates acantholysis. Furthermore, the possible suppliers of the Fas pathway were investigated. METHODS: Seventeen biopsies of pemphigus patients were studied by haematoxylin and eosin staining, and apoptosis was defined by TUNEL. The expression of Fas, FasL and caspase 3 was studied by in situ hybridization and immunohistochemistry. Cell infiltrates were studied by immunofluorescence with monoclonal anti-CD3, CD4, CD8, CD19 and CD69. RESULTS: All of the biopsies showed intra-epidermal blisters, acantholytic cells and inflammatory infiltrates. The blisters expressed Fas, FasL and caspase 3. Cell infiltrates were composed of CD8 and a few CD4(+)CD69(+) cells. Additionally, CD19(+) cells were detected. Interestingly, the Fas expression was increased in acantholytic cells and perilesional keratinocytes. Incidentally, these cells exhibited apoptotic features. Interestingly, the CD8 cells expressed FasL. CONCLUSION: This paper presents the morphological evidence that apoptosis and acantholysis are linked. Therefore, the Fas pathway is associated with CD8 cells in pemphigus lesions.
Assuntos
Acantólise/patologia , Pênfigo/patologia , Receptor fas/fisiologia , Adulto , Sequência de Bases , Biópsia , Primers do DNA , Feminino , Imunofluorescência , Humanos , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , Masculino , Reação em Cadeia da PolimeraseRESUMO
The present investigation assesses the possible role of apoptosis and necrosis in intracellular antigen exposure of kidneys from Balb/c mice. Renal tissues were cultured and treated with chemicals to induce apoptosis and /or necrosis. The expression of intracellular antigens Sm, RNP, Ro and La were monitored with antibodies against these antigens. Main results confirm that renal intracellular antigens are released and exposed onto the surface of apoptotic and necrotic cells, therefore these antigens become an easy target of autoantibodies. This mechanism may be important in the lupus nephritis pathogenesis.
Assuntos
Autoantígenos/biossíntese , Rim/imunologia , Rim/patologia , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Ribonucleoproteínas/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Necrose/induzido quimicamente , Técnicas de Cultura de Tecidos , Proteínas Centrais de snRNP , Antígeno SS-BRESUMO
Apoptosis is the physiologic process that guarantees the cellular exchange; after apoptosis the cellular remains are cleared by phagocytosis. In autoimmunity, some mechanisms in apoptosis fail and may result in disease. For instance, a failure in the Fas pathway during lymphoid ontogeny may allow the survival of autoimmune clones; equally the lack of clearance of apoptotic corps containing self-antigens may activate pre-existent auto-reactive clones and may result in autoantibody production. The role of apoptosis in autoimmunity is reviewed.
Assuntos
Apoptose/imunologia , Autoanticorpos/biossíntese , HumanosRESUMO
Scleroderma is an autoimmune disease characterized by early inflammatory infiltrates followed by fibrosis in the skin and internal organs. CREST is a relatively benign cutaneous variant of scleroderma that features calcinosis, Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly and telangiectases. Glomerulonephritis is a rare association of CREST. We are reporting a patient with CREST who developed glomerulonephritis and had anticentromere and antineutrophil cytoplasmic autoantibodies (ANCA) in her serum.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Síndrome CREST/diagnóstico , Glomerulonefrite por IGA/diagnóstico , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/imunologia , Anticorpos Anticitoplasma de Neutrófilos/análise , Biópsia por Agulha , Síndrome CREST/complicações , Síndrome CREST/terapia , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Seguimentos , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Imuno-Histoquímica , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Peroxidase/análise , Peroxidase/imunologia , Medição de Risco , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Pemphigus is an autoimmune disease characterized by intraepidermal blisters induced by pemphigus IgG. In addition to autoantibodies, molecular mechanisms involved in acantholysis remain largely unknown. For this reason, we address a possible role of the inflammatory cytokines IL-6 and TNFalpha in pemphigus lesions. METHODS: Sixteen biopsies from patients with different types of pemphigus were studied by in situ hybridization using DNA fluorescent probes for IL-6 and TNFalpha mRNA. RESULTS: Fifty-six percent of lesional biopsies exhibited cytokine gene expression, which was poorly expressed in noninvolved skin. Deposits of TNFalpha and IL-6 were products of in situ transcription at the epidermal level. CONCLUSIONS: Inflammatory cytokine expression around the blister could play a mediator role in pemphigus lesions by increasing epithelial damage.
Assuntos
Vesícula/patologia , Interleucina-6/genética , Pênfigo/patologia , Fator de Necrose Tumoral alfa/genética , Biópsia , Vesícula/fisiopatologia , Humanos , Hibridização in Situ Fluorescente , Interleucina-6/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pele/metabolismo , Pele/patologia , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
The cellular localization of the Ro/SS-A antigen was defined using indirect immunofluorescence and eight monospecific anti- Ro/SS-A antisera which were identified by immunoblotting. Several mammalian tissues were used as substrates. The Ro/SS-A antigen was located mainly in the nucleus of dog liver and Hep-2-cells, and anti-Ro sera had produced a speckled staining pattern. Cytoplasmic fluorescence appeared only in one serum. IgG was the predominant immunoglobulin with anti-Ro/SS-A activity; five sera had complement fixing activity. The sera absorption studies with partially purified Ro/SS-A antigen and the negativation of the ANA tests had confirmed the specificity of our findings.