RESUMO
Acute rheumatic fever (ARF) is an autoimmune sequela of group A streptococcal infection mostly affecting school-aged children. Recurrent episodes of ARF can result in the development of rheumatic heart disease (RHD). One in 40 indigenous Australians in the Northern Territory is affected by RHD. This disease mostly impacts young people; 45% of those who require heart valve surgery in Australia due to RHD are younger than 25 years old. ARF is characterized by autoimmune attack of the heart; therefore, the presence of the autoantibodies involved could potentially be used to diagnose ARF. To this end, a human heart cDNA library was screened with serum from a patient with ARF, and 12 autoreactive human heart antigens were identified. They include five different IgG heavy chains and a range of tissue-specific cell-signaling proteins, species of which have been implicated in other autoimmune diseases. Preliminary ELISA results show that ARF patients have significantly higher levels of antibodies recognizing the cardiac autoantigens than controls. These antigens are promising candidates for the development of a serological assay for the diagnosis of ARF. The nature of the proteins identified has exciting implications for future research into the pathogenesis of ARF.
Assuntos
Autoantígenos/imunologia , Biblioteca Gênica , Miocárdio/metabolismo , Febre Reumática/sangue , Doença Aguda , Adulto , Proteínas de Transporte/imunologia , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular , DNA Complementar/genética , DNA Complementar/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Escherichia coli/genética , Humanos , Cadeias Pesadas de Imunoglobulinas/imunologia , Cadeias Pesadas de Imunoglobulinas/metabolismo , Complexo Mediador , Proteínas dos Microfilamentos/imunologia , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Cadeias Leves de Miosina/imunologia , Cadeias Leves de Miosina/metabolismo , Proteínas do Tecido Nervoso/imunologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/imunologia , Proteínas Nucleares/metabolismo , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Febre Reumática/diagnóstico , Febre Reumática/imunologia , Fatores de Transcrição/imunologia , Fatores de Transcrição/metabolismo , alfa Catenina/imunologia , alfa Catenina/metabolismoAssuntos
Antioxidantes/metabolismo , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiologia , Enterococcus faecalis/patogenicidade , Pseudomonas aeruginosa/patogenicidade , Espécies Reativas de Oxigênio/metabolismo , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Enterococcus faecalis/metabolismo , Genes de Helmintos , Peróxido de Hidrogênio/metabolismo , Longevidade , Mutação , Pseudomonas aeruginosa/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/fisiologia , Superóxidos/metabolismoRESUMO
Recently, we reported that Streptococcus pyogenes kills Caenorhabditis elegans by the use of hydrogen peroxide (H2O2). Here we show that diverse streptococcal species cause death of C. elegans larvae in proportion to the level of H2O2 produced. H2O2 may mask the effects of other pathogenicity factors of catalase-negative bacteria in the C. elegans infection model.
