Abstract
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.
