Autoantigenic epitopes on DNA topoisomerase I. Clinical and immunogenetic associations in systemic sclerosis.
OBJECTIVE
To elucidate the clinical and immunogenetic associations with reactivity to autoantigenic epitopes on DNA topoisomerase I (topo I) recognized by sera from patients with systemic sclerosis (SSc).


METHODS
Autoantigenic epitopes on topo I were identified by screening an epitope library constructed from topo I complementary DNA restriction fragments using autoimmune anti-topo I-positive sera as a probe. Epitope reactivities of sera from 43 anti-topo I-positive SSc patients were surveyed by immunoblotting, and associations with clinical symptoms and HLA-DR types were examined.


RESULTS
Four different epitope regions were identified on the topo I molecule. Immunoreactivity to the region encompassing amino acid residues 658-700, termed ER4, was found to be associated with diffuse cutaneous SSc, progressive pulmonary interstitial fibrosis, and poor prognosis for 15-year survival. SSc patients with ER4 reactivity frequently displayed the DR2/DRw52 phenotype.


CONCLUSIONS
Molecular analysis of precise antigenic epitopes on topo I is helpful in classifying clinical subsets of SSc.
Kuwana
M
M
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Kaburaki
J
J
Mimori
T
T
Tojo
T
T
Homma
M
M
D000328:Adult; D001324:Autoantigens / Q000276:immunology*; D001483:Base Sequence; D001769:Blood / Q000276:immunology; D002423:Cause of Death; D004264:DNA Topoisomerases, Type I / Q000276:immunology*; D000939:Epitopes; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D011379:Prognosis; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D016019:Survival Analysis
D001324:Autoantigens; D000939:Epitopes; D006684:HLA-DR Antigens; D015345:Oligonucleotide Probes; D004264:DNA Topoisomerases, Type I