RESUMO
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Assuntos
Humanos , Masculino , Adulto , Actinas/imunologia , Reações Cruzadas/imunologia , Hipersensibilidade Alimentar/imunologia , Alérgenos/isolamento & purificação , Frutose-Bifosfato Aldolase/efeitos adversos , Testes Cutâneos/métodos , Fosfopiruvato Hidratase/efeitos adversos , Carne/efeitos adversos , Produtos Pesqueiros/efeitos adversosAssuntos
Hipersensibilidade Alimentar/imunologia , Hipersensibilidade ao Látex/imunologia , Lycium/imunologia , Fosfopiruvato Hidratase/imunologia , Prurido/imunologia , beta-Glucosidase/imunologia , Adulto , Alérgenos/efeitos adversos , Alérgenos/imunologia , Proteínas de Transporte/efeitos adversos , Proteínas de Transporte/imunologia , Feminino , Hipersensibilidade Alimentar/diagnóstico , Frutas/efeitos adversos , Humanos , Imunoglobulina E/sangue , Látex/efeitos adversos , Hipersensibilidade ao Látex/diagnóstico , Fosfopiruvato Hidratase/efeitos adversos , Fosfopiruvato Hidratase/isolamento & purificação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Prurido/diagnóstico , Prurido/etiologia , Testes Cutâneos , Síndrome , beta-Glucosidase/efeitos adversos , beta-Glucosidase/isolamento & purificaçãoRESUMO
OBJECTIVE: To examine the hypothesis that the subset of rheumatoid arthritis (RA) characterized by antibodies to citrullinated α-enolase is mediated by Porphyromonas gingivalis enolase in the context of DR4 alleles. METHODS: Recombinant human α-enolase and P gingivalis enolase, either citrullinated or uncitrullinated, were used to immunize DR4-IE-transgenic mice and control mice (class II major histocompatibility complex-deficient [class II MHC(-/-)] and C57BL/6 wild-type mice). Arthritis was quantified by measurement of ankle swelling in the hind paws and histologic examination. Serum IgG reactivity with α-enolase and citrullinated α-enolase was assayed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Antibodies to peptide 1 of citrullinated α-enolase (CEP-1) and its arginine-bearing control peptide, REP-1, were also assessed by ELISA. RESULTS: Significant hind-ankle swelling (≥0.3 mm) occurred in DR4-IE-transgenic mice immunized with citrullinated human α-enolase (9 of 12 mice), uncitrullinated human α-enolase (9 of 12 mice), citrullinated P gingivalis enolase (6 of 6 mice), and uncitrullinated P gingivalis enolase (6 of 6 mice). Swelling peaked on day 24. None of the control groups developed arthritis. The arthritic joints showed synovial hyperplasia and erosions, but there was a paucity of leukocyte infiltration. Antibodies to human α-enolase, both citrullinated and unmodified, and to CEP-1 and REP-1 were detectable in all immunized mice except the class II MHC(-/-) control mice. CONCLUSION: This is the first animal model that links an immune response to P gingivalis enolase to an important subset of RA, defined by antibodies to citrullinated α-enolase in the context of DR4. The fact that arthritis and anti-CEP-1 antibodies were induced independent of citrullination of the immunizing antigen suggests that the unmodified form of α-enolase may be important in initiating the corresponding subset of human RA.
