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Infliximab induced anti-dsDNA: characteristics of autoantibody response

We have previously been reported that 7–12% of patients with rheumatoid arthritis develop IgM anti-dsDNA following treatment with infliximab and that lupus was observed in 1 of 156 patients and was associated with and IgG and an IgM anti-dsDNA response (Charles et al. Arthritis Rheum 2000, 43:2883–2900). In this study we examine the characteristics of the autoantibody response to find evidence for the involvement of potential mechanisms including upregulated synthesis of natural autoantibodies, polyclonal IgM activation, the production of cross reactive rheumatoid factors, or a response to apoptotic release of nucleosomal material.

Methods

IgM antibodies to IgG (rheumatoid factor), mitochondrial, microsomal, measles antigens and circulating nucleosome levels were measured prior to and following infliximab therapy. Sera containing induced anti-dsDNA antibodies were studied by immunofluorescent inhibition to examine cross reactivity.

Results

  • IgM antibodies to mitochondrial, microsomal and measles antigens were unchanged following infliximab therapy (pretreatment vs. post-8 weeks=ns).

  • IgM anti-dsDNA were inhibited by dsDNA, but not by rabbit or human IgG, or histones.

  • Levels of circulating nucleosomes fell following infliximab therapy (pre-treatment vs. post-2 weeks P ≤ 0.02; vs. post-4 weeks P ≤ 0.05).

Conclusion

We were unable to find any evidence to support a role for upregulation of IgM natural autoantibodies, a polyclonal increase in IgM antibodies, cross reactive rheumatoid factors, or nucleosome release and consequent antigen drive. The induction of anti-dsDNA antibodies appears to be dependent on an, as yet, ill understood mechanism.

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Charles, P., Aarden, L. & Maini, R. Infliximab induced anti-dsDNA: characteristics of autoantibody response. Arthritis Res Ther 4 (Suppl 1), 73 (2002). https://doi.org/10.1186/ar518

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  • DOI: https://doi.org/10.1186/ar518

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