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Autoimmune Response to Proteins of Proliferating Cell Nuclear Antigen Multiprotein Complexes in Patients with Connective Tissue Diseases
KAZUHIKO KANEDA, YOSHINARI TAKASAKI, KEN TAKEUCHI, HIROFUMI YAMADA, MASUYUKI NAWATA, MASAKAZU MATSUSHITA, RAN MATSUDAIRA, KEIGO IKEDA, KENJIRO YAMANAKA, and HIROSHI HASHIMOTO
ABSTRACT. Methods. The PCNA complex was purified by affinity chromatography using anti-PCNA monoclonal antibodies. Then 196 serum samples from patients with systemic lupus erythematosus (SLE) and 82 from patients with other CTD were tested for reactivity with the complex by immunoblotting. Results. Of 196 SLE sera, 61 (31%) reacted with at least one component of the PCNA complex, and most reactive sera contained autoantibodies to several components of the complex. Autoantibodies to PCNA complex were less common in patients with other CTD, and most of their sera reacted only with one or a few proteins in the complex. Two out of 20 scleroderma sera reactive with 100, 85, and 70 kDa proteins in the PCNA complex also had autoantibodies to topoisomerase I (topo I) antibodies, which is an element of the complex. These findings suggest that the autoimmune response to the PCNA complex was specific for SLE. Anti-PCNA complex antibodies were associated with an increased serum level of PCNA detected by ELISA. The spreading of the autoimmune response to the elements of the complex was observed in parallel with the increased serum PCNA level when a series of sera from a lupus patient were tested longitudinally. In addition, anti-PCNA complex antibodies were significantly correlated with lupus erythematosus cells. Conclusion. The "antigen-driven" system may play a crucial role in inducing the autoimmune response to the PCNA complex in patients with SLE. (J Rheumatol 2004;31:2142-50) Key Indexing Terms:
SYSTEMIC LUPUS ERYTHEMATOSUS
From the Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine; and the Department of Internal Medicine, Kyoundo Hospital, Tokyo, Japan. Supported in part by a Grant-in-Aid for Scientific Research of the Ministry of Education and Science (No. 13670476). K. Kaneda, MD; Y. Takasaki, MD; K. Takeuchi, MD; H. Yamada, MD; M. Nawata, MD; M. Matsushita, MD; R. Matsudaira, MD; K. Ikeda, MD, Juntendo University School of Medicine; K. Yamanaka, MD, Juntendo University School of Medicine and Kyoundo Hospital; H. Hashimoto, MD, Juntendo University School of Medicine. Address reprint requests to Dr. Y. Takasaki, Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: tyoshi@med.juntendo.ac.jp Submitted March 9, 2004; revision accepted May 26, 2004. |