S Sato1, M Kodera, M Hasegawa, M Fujimoto, K Takehara. 1. Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. s-sato@net.nagasaki-u.ac.jp
Abstract
BACKGROUND: Localized scleroderma (LSc) exhibits autoimmunity, and antihistone antibody is frequently detected. The major antigens recognized by antihistone antibody are histones H1, H2A and H2B, which are located on the outer side of the nucleosome and are relatively more accessible for antibody binding. Therefore, it has been hypothesized that antihistone antibody is induced by nucleosome or native chromatin as immunogens in LSc. OBJECTIVES: To determine whether antinucleosome antibody is present in patients with LSc. METHODS: Antinucleosome antibody, antihistone antibody and antidouble-stranded DNA (dsDNA) antibody were determined by enzyme-linked immunosorbent assay. Results IgG or IgM antinucleosome antibody was detected more frequently in patients with LSc than was antihistone antibody: in 40 of 49 (82%) vs. 26 of 49 (53%), respectively. No patients had anti-dsDNA antibody. The prevalence of antinucleosome antibody positivity was comparable in the three subgroups of LSc (generalized morphoea, 89%; linear scleroderma, 71%; morphoea, 90%). Patients with systemic lupus erythematosus (SLE) exhibited a similar frequency of antinucleosome antibody positivity (13 of 15, 87%), but their IgG levels of this autoantibody were much higher than those found in patients with LSc. By contrast, IgM antinucleosome antibody levels were normal in patients with SLE, while they were significantly increased in patients with LSc compared with normal controls. Antinucleosome antibody was also detected at lower frequency in patients with systemic sclerosis (five of 20, 25%) or dermatomyositis (five of 15, 33%). Nucleosome-restricted antibodies, i.e. antibodies that react with the whole nucleosome particle but not with its individual components (histones and dsDNA) were also present in 35% of patients with LSc. CONCLUSIONS: Although antinucleosome antibody was not specific to LSc, its high prevalence in LSc indicates that antinucleosome antibody is a major autoantibody in this disease.
BACKGROUND:Localized scleroderma (LSc) exhibits autoimmunity, and antihistone antibody is frequently detected. The major antigens recognized by antihistone antibody are histones H1, H2A and H2B, which are located on the outer side of the nucleosome and are relatively more accessible for antibody binding. Therefore, it has been hypothesized that antihistone antibody is induced by nucleosome or native chromatin as immunogens in LSc. OBJECTIVES: To determine whether antinucleosome antibody is present in patients with LSc. METHODS: Antinucleosome antibody, antihistone antibody and antidouble-stranded DNA (dsDNA) antibody were determined by enzyme-linked immunosorbent assay. Results IgG or IgM antinucleosome antibody was detected more frequently in patients with LSc than was antihistone antibody: in 40 of 49 (82%) vs. 26 of 49 (53%), respectively. No patients had anti-dsDNA antibody. The prevalence of antinucleosome antibody positivity was comparable in the three subgroups of LSc (generalized morphoea, 89%; linear scleroderma, 71%; morphoea, 90%). Patients with systemic lupus erythematosus (SLE) exhibited a similar frequency of antinucleosome antibody positivity (13 of 15, 87%), but their IgG levels of this autoantibody were much higher than those found in patients with LSc. By contrast, IgM antinucleosome antibody levels were normal in patients with SLE, while they were significantly increased in patients with LSc compared with normal controls. Antinucleosome antibody was also detected at lower frequency in patients with systemic sclerosis (five of 20, 25%) or dermatomyositis (five of 15, 33%). Nucleosome-restricted antibodies, i.e. antibodies that react with the whole nucleosome particle but not with its individual components (histones and dsDNA) were also present in 35% of patients with LSc. CONCLUSIONS: Although antinucleosome antibody was not specific to LSc, its high prevalence in LSc indicates that antinucleosome antibody is a major autoantibody in this disease.
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