Anti‐DNA topoisomerase IIα autoantibodies in localized scleroderma

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Abstract
Objective: To determine the prevalence and clinical correlation of anti‐DNA topoisomerase IIα (anti–topo IIα) antibody in patients with localized scleroderma.Methods: Anti–topo IIα antibodies or anti‐DNA topoisomerase I (topo I) antibodies were determined by enzyme‐linked immunosorbent assay (ELISA) and immunoblotting. Inhibition of topo IIα enzymatic activity by the antibodies was evaluated by decatenation assays using kinetoplast DNA as a substrate.Results: IgG or IgM anti–topo IIα 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 IIα antibody in sera from patients with localized scleroderma and showed no cross‐reactivity of anti–topo IIα 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 IIα. The presence of anti–topo IIα antibody was associated with a greater total number of sclerotic lesions and number of plaque lesions in patients with localized scleroderma. Furthermore, anti–topo IIα antibody was able to inhibit topo IIα enzymatic activity.Conclusion: The results of the present study indicate that anti–topo IIα is a major autoantibody in localized scleroderma, and is distinct from anti–topo I antibody in SSc.