Anti-DNA topoisomerase IIalpha autoantibodies in localized scleroderma.
OBJECTIVE
To determine the prevalence and clinical correlation of anti-DNA topoisomerase IIalpha (anti-topo IIalpha) antibody in patients with localized scleroderma.


METHODS
Anti-topo IIalpha antibodies or anti-DNA topoisomerase I (topo I) antibodies were determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Inhibition of topo IIalpha enzymatic activity by the antibodies was evaluated by decatenation assays using kinetoplast DNA as a substrate.


RESULTS
IgG or IgM anti-topo IIalpha antibody was detected in 76% (35 of 46) of patients with localized scleroderma, and in 85% (11 of 13) of patients with generalized morphea, the severest form of localized scleroderma. This prevalence of the antibody in patients with localized scleroderma was much higher than that found in patients with systemic sclerosis (SSc) (5 of 37 [14%]), systemic lupus erythematosus (2 of 26 [8%]), dermatomyositis (2 of 20 [10%]), and in healthy controls (3 of 42 [7%]). Immunoblotting confirmed the presence of IgG anti-topo IIalpha antibody in sera from patients with localized scleroderma and showed no cross-reactivity of anti-topo IIalpha antibody with topo I. Anti-topo I antibody was not detected by ELISA in any sera from patients with localized scleroderma. In addition, anti-topo I antibody from SSc patients did not cross-react with topo IIalpha. The presence of anti-topo IIalpha antibody was associated with a greater total number of sclerotic lesions and number of plaque lesions in patients with localized scleroderma. Furthermore, anti-topo IIalpha antibody was able to inhibit topo IIalpha enzymatic activity.


CONCLUSIONS
The results of the present study indicate that anti-topo IIalpha is a major autoantibody in localized scleroderma, and is distinct from anti-topo I antibody in SSc.
Hayakawa
Ikuko
I
Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Hasegawa
Minoru
M
Takehara
Kazuhiko
K
Sato
Shinichi
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood*; D000951:Antigens, Neoplasm; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D004250:DNA Topoisomerases, Type II / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins; D004789:Enzyme Activation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D012594:Scleroderma, Localized / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism; D016036:Seroepidemiologic Studies
D000974:Antibodies, Antinuclear; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D004250:DNA Topoisomerases, Type II