Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Food Hypersensitivity/diagnosis , Seafood/adverse effects , Fishes , Phosphopyruvate Hydratase/adverse effects , Allergens , Skin TestsABSTRACT
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Subject(s)
Humans , Male , Adult , Actins/immunology , Cross Reactions/immunology , Food Hypersensitivity/immunology , Allergens/isolation & purification , Fructose-Bisphosphate Aldolase/adverse effects , Skin Tests/methods , Phosphopyruvate Hydratase/adverse effects , Meat/adverse effects , Fish Products/adverse effectsSubject(s)
Food Hypersensitivity/immunology , Latex Hypersensitivity/immunology , Lycium/immunology , Phosphopyruvate Hydratase/immunology , Pruritus/immunology , beta-Glucosidase/immunology , Adult , Allergens/adverse effects , Allergens/immunology , Carrier Proteins/adverse effects , Carrier Proteins/immunology , Female , Food Hypersensitivity/diagnosis , Fruit/adverse effects , Humans , Immunoglobulin E/blood , Latex/adverse effects , Latex Hypersensitivity/diagnosis , Phosphopyruvate Hydratase/adverse effects , Phosphopyruvate Hydratase/isolation & purification , Plant Extracts/administration & dosage , Plant Extracts/adverse effects , Pruritus/diagnosis , Pruritus/etiology , Skin Tests , Syndrome , beta-Glucosidase/adverse effects , beta-Glucosidase/isolation & purificationABSTRACT
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.
