Pa. Henry et al., Diversity and plasticity of the anti-DNA topoisomerase I autoantibody response in scleroderma, ARTH RHEUM, 43(12), 2000, pp. 2733-2742
Objective. To examine domain recognition by anti-DNA topoisomerase I (anti-
DNA topo I, or anti-topo I) antibodies over time in scleroderma patients.
Methods. Serial serum samples from scleroderma patients with known reactivi
ty to Scl-70, a 70-kd topo I breakdown product, were tested by immunoblot f
or IgM, IgG, IgA, kappa, and lambda reactivity to Scl-70 and 8 overlapping
recombinant peptide fragments (F1-F8) that span the human topo I molecule.
Results, IgM, IgG, kappa, and lambda anti-topo I antibodies in both early-d
isease and late-disease serum samples preferentially recognized the Scl-70
molecule rather than the F1-F8 peptides, suggesting preferential recognitio
n of conformational determinants on Scl-70 throughout the disease course. A
mounts of both primary and secondary anti-topo I antibodies to Scl-70 varie
d over time, including increases in primary antibody responses late in the
disease course. Striking variability in recognition of the F1-F8 peptides b
y IgM, IgG, IgA, kappa, and lambda anti-topo I antibodies was seen in seria
l samples. Most often, the change in FI-FS recognition from one sample to t
he next was unpredictable, although occasionally patterns of antibody recog
nition were reciprocal in serial samples. Of note, in several patients, wha
t could have been interpreted as domain spreading among F1-F8 in 2 successi
ve samples was just a part of changing antibody reactivity to these peptide
s that again became more restricted in a third sample.
Conclusion. Titers and immunodominant domains recognized by both primary an
d secondary anti-topo I antibodies are highly variable over time. This sugg
ests continual antigen presentation and regulation of the anti-topo I antib
ody response in scleroderma, even late in the disease course.