Exposure to nuclear antigens contributes to the induction of humoral autoimmunity during tumour necrosis factor alpha blockade

Autor: Timothy B. Niewold, P. P. Tak, Mary K. Crow, Carla A. Wijbrandts, Clio P. Mavragani, Dominique Baeten, T Niers, Bernard Vandooren, Tineke Cantaert, Eric Veys, D Richel, L De Rycke
Přispěvatelé: Clinical Immunology and Rheumatology, Center of Experimental and Molecular Medicine, CCA -Cancer Center Amsterdam, Oncology, AII - Amsterdam institute for Infection and Immunity, Faculteit der Geneeskunde
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Male
Anti-nuclear antibody
Apoptosis
medicine.disease_cause
Receptors
Tumor Necrosis Factor
Etanercept
Autoimmunity
Interferon
immune system diseases
Immunology and Allergy
Medicine
skin and connective tissue diseases
TUNEL assay
Synovial Membrane
Antibodies
Monoclonal
Complement C4
Complement C3
Middle Aged
Nucleosomes
Antibodies
Antinuclear
Antirheumatic Agents
Interferon Type I
Female
medicine.drug
Adult
musculoskeletal diseases
medicine.medical_specialty
Immunology
General Biochemistry
Genetics and Molecular Biology
Statistics
Nonparametric
Article
Young Adult
Rheumatology
Internal medicine
Spondylarthritis
Humans
Aged
Autoantibodies
business.industry
Infliximab
stomatognathic diseases
Immunoglobulin M
Immunoglobulin G
Humoral immunity
Antibody Formation
Tumor Necrosis Factor Inhibitors
business
Zdroj: Annals of the rheumatic diseases, 68(6), 1022-1029. BMJ Publishing Group
Annals of the Rheumatic Diseases, 68(6), 1022-1029. BMJ Publishing Group
ISSN: 0003-4967
Popis: Objective: Type I interferons and apoptotic particles contribute to antinuclear autoimmunity in experimental models. This study assessed whether similar mechanisms contribute to break peripheral B-cell tolerance in humans by studying the induction of antinuclear antibodies by tumour necrosis factor blockade in spondyloarthritis. Methods: 40 spondyloarthritis patients treated with infliximab or etanercept and 20 renal cell carcinoma patients treated with sorafenib were studied. Serum antinucleosome IgM and nucleosomes were measured by ELISA. Type I interferon serum activity was measured using a functional reporter cell assay. Synovial apoptosis was assessed by terminal transferase nick end-labelling (TUNEL) assay and anti-active caspase-3 immunostaining. Complement was measured by nephelometry. Results: Despite a similar clinical improvement and reduction of synovial inflammation, antinucleosome IgM were induced by infliximab but not etanercept. This induction did not correlate with type I interferon activity, which was transiently downmodulated by infliximab but persistently upregulated by etanercept. In contrast, antinucleosome IgM levels did correlate with serum nucleosome levels, which were significantly upregulated by infliximab but not by etanercept treatment. This increase in serum nucleosome levels was not directly related to massive cell death, but rather to a decrease of complement 3 and 4 serum levels during infliximab treatment. Conclusion: Infliximab and etanercept have a differential effect on both type I interferon activity and nucleosome levels. Only elevated serum nucleosomes relate to the induction of antinucleosome antibodies after infliximab treatment.
Databáze: OpenAIRE
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