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

T. Cantaert, L. De Rycke, C. P. Mavragani, C. A. Wijbrandts, T. B. Niewold, T. Niers, B. Vandooren, E. M. Veys, D. Richel, P. P. Tak, M. K. Crow, D. Baeten

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1022-1029
Number of pages8
JournalAnnals of the rheumatic diseases
Volume68
Issue number6
DOIs
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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    Cantaert, T., De Rycke, L., Mavragani, C. P., Wijbrandts, C. A., Niewold, T. B., Niers, T., Vandooren, B., Veys, E. M., Richel, D., Tak, P. P., Crow, M. K., & Baeten, D. (2009). Exposure to nuclear antigens contributes to the induction of humoral autoimmunity during tumour necrosis factor alpha blockade. Annals of the rheumatic diseases, 68(6), 1022-1029. https://doi.org/10.1136/ard.2008.093724