Abstract
The pathogenesis and etiology of systemic sclerosis (SSc) remain unknown, but the presence of several autoantibodies is recognized as one of its prominent features. The clinical significance of anti-DNA topoisomerase II α antibody (anti-topo II α Ab) remains unknown in Japanese patients with SSc. To determine the prevalence and clinical correlation of anti-topo II α Ab in Japanese patients with SSc. Serum samples were obtained from 103 Japanese patients with SSc. Control serum samples were obtained from 43 healthy Japanese volunteers. Anti-topo II α Abs were determined by enzyme linked-immunosorbent assay.IgG anti-topo II α Ab levels were significantly increased in SSc patients (n=103) compared to normal controls (n=43; P<0.005). IgG or IgM anti-topo II α Ab was detected in 19% (20/103) of SSc patients when absorbance values higher than the mean+2SD of control serum samples were considered positive. By contrast, IgG or IgM anti-topo II α Ab was observed in only 7% (3/43) of healthy individuals. The presence of pulmonary fibrosis was more frequently detected in SSc patients with IgG anti-topo II α Ab than those without the Ab (P<0.05). Moreover, % DLco and % VC were significantly decreased in SSc patients with anti-topo II α Ab relative to those without the Ab (P<0.05 and P<0.01, respectively). The elevated levels of both erythrocyte sedimentation rate and C-reactive protein were also more frequently observed in SSc patients positive for IgG anti-topo II α Ab (P<0.005). The results of the present study indicate that anti-topo II α Ab represent one of the autoantibody specificities detected on SSc patients and may be regarded a serological marker of pulmonary fibrosis in Japanese patients with SSc.
References
Grigolo B, Mazzetti I, Borzi RM, Hickson ID, Fabbri M, Fasano L, Meliconi R, Facchini A (1998) Mapping of topoisomerase II α epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis. Clin Exp Immunol 114:339–346
Grigolo B, Mazzetti I, Meliconi R, Bazzi S, Scorza R, Candela M, Gabrielli A, Facchini A (2000) Anti-topoisomerase II α autoantibodies in systemic sclerosis-association with pulmonary hypertension and HLA-B35. Clin Exp Immunol 121:539–543
Hayakawa I, Hasegawa M, Takehara K, Sato S (2004) Anti-DNA topoisomerase IIα autoantibodies in localized scleroderma. Arthritis Rheum 50:227–232
Chang YH, Hwang J, Shang HF, Tsai ST (1996) Characterization of human DNA topoisomerase II as an autoantigen recognized by patients with IDDM. Diabetes 45:408–414
Zuklys KL, Szer IS, Szer W (1991) Autoantibodies to DNA topoisomerase II in juvenile rheumatoid arthritis. Clin Exp Immunol 84:245–249
Hoffmann A, Heck MM, Bordwell BJ, Rothfield NF, Earnshaw WC (1989) Human autoantibody to topoisomerase II. Exp Cell Res 180:409–418
Meliconi R, Bestagno M, Sturani C, Negri C, Galavotti V, Sala C, Facchini A, Ciarrocchi G, Gasbarrini G, Astaldi Ricotti GC (1989) Autoantibodies to DNA topoisomerase II in cryptogenic fibrosing alveolitis and connective tissue disease. Clin Exp Immunol 76:184–189
Kuwana M, Okano Y, Kaburaki J, Tojo T, Medsger TA Jr (1994) Racial differences in the distribution of systemic sclerosis-related serum antinuclear antibodies. Arthritis Rheum 37:902–906
Kuwana M, Kaburaki J, Arnett FC, Howard RF, Medsger TA, Jr, Wright TM (1999) Influence of ethnic background on clinical and serologic features in patients with systemic sclerosis and anti-DNA topoisomerase I antibody. Arthritis Rheum 42:465–474
Subcommittee for Scleroderma Criteria of the American Rhematism Association Diagnostic and Therapeuric Criteria Committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581–590
LeRoy EC, Krieg T, Black C, Medsger TAJ, Fleischmajer R, Rowell N, Jablonska S, Wollheim F (1988) Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis. J Rheumatol 15:202–205
Steen VD, Powell DL, Medsger TAJ (1988) Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis. Arthritis Rheum 31:196–203
Sato S, Ihn H, Soma Y, Igarashi A, Tamaki T, Kikuchi K, Ishibashi Y, Takehara K (1993) Antihistone antibodies in patients with localized scleroderma. Arthritis Rheum 36:1137–1141
Silver RM (1996) Clinical problems: the lungs. Rheum Dis Clin Nor Am 22:825–840
LeRoy EC (1974) Increased collagen synthesis by scleroderma skin fibroblasts in vitro: a possible defect in the regulation or activation of the scleroderma fibroblast. J Clin Invest 54:880–889
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by a grant-in-aid from the Ministry of Health and Welfare of Japan (to Minoru Hasegawa and Shinichi Sato)
Rights and permissions
About this article
Cite this article
Hayakawa, I., Hasegawa, M., Takehara, K. et al. Anti-DNA topoisomerase II α autoantibodies in Japanese patients with systemic sclerosis. Arch Dermatol Res 297, 180–183 (2005). https://doi.org/10.1007/s00403-005-0603-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-005-0603-7