The emergence of anti-dsDNA antibodies precedes nucleosome-specific antibodies in MRL/lpr and MRL/+ mice

DOI 機関リポジトリ 被引用文献1件
  • Qing Lu
    Tokyo Medical and Dental University Graduate School of Allied Health Sciences, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
  • Kanai Yoshiyuki
    Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan
  • Kubota Tetsuo
    Tokyo Medical and Dental University Graduate School of Allied Health Sciences, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan

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Nucleosome (NS)-reactive autoantibodies appear to be involved in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanisms responsible for their production remain elusive. To study whether antibodies specific to NS are present prior to anti-double-stranded (ds) DNA antibodies in lupus mice, ELISA was carried out using the plates which had been confirmed to be coated with comparable amounts of oligo-NS and dsDNA. IgG antibodies reactive with NS or dsDNA were both detected as early as 6 weeks and 10 weeks of age in MRL/lpr and MRL/+ mice, respectively. Their titers increased with age. The specificity of dsDNA binding activity in these young mice was confirmed by the finding that their sera reacted not only with mammalian dsDNA but also with dsDNA from different sources including synthetic polynucleotides. On the other hand, NS binding activity in young mice could be ascribed to cross-reactivity of the antidsDNA antibodies, because it was completely inhibited by free dsDNA. A role for NS or chromatin in triggering the production of anti-dsDNA antibodies has recently been suggested, but the present results argue that, at least in these strains of mice, antibodies specifically recognizing conformational epitopes on NS are not produced before those specific to dsDNA.

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