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Autoimmune Response to Proteasome Activator 28a in Patients with Connective Tissue Diseases
MASAKAZU MATSUSHITA, YOSHINARI TAKASAKI, KEN TAKEUCHI, HIROFUMI YAMADA, RAN MATSUDAIRA, and HIROSHI HASHIMOTO
ABSTRACT.
Methods. Serum samples were obtained from 219 patients with various connective tissue diseases. cDNA encoding full-length human PA28α and Ki were produced by polymerase chain reaction. Antigens were expressed as glutathione S-transferase (GST) fusion proteins. The immunoreactivity of serum for PA28α and Ki was studied by Western blotting. An inhibition test was performed by ELISA using purified Ki antigen. Results. Anti-PA28α> antibody was detected in serum from 23% of patients with systemic lupus erythematosus (SLE) and 24% with Sjögren's syndrome (SS). These rates were significantly higher than those for the other rheumatic diseases. Since both PA28α and Ki are elements of the PA28 complex and their amino acid sequences share 40.2% homology, immunoreactivity to PA28α was studied further. Among 27 anti-Ki positive serum samples, 13 samples (48%) also reacted with PA28α, suggesting a relationship between anti-PA28α and anti-Ki antibodies. To investigate whether this finding was due to the presence of cross-reacting epitopes for PA28α and Ki antigens, an inhibition test was performed by ELISA. The reactivity to purified Ki antigen was not inhibited by preincubation with recombinant PA28α. Conclusion. Detection of anti-PA28α antibody was significantly higher in serum from patients with SLE and SS. The relationship between anti-PA28α and Ki antibodies suggests the importance of an antigen-driven system in the induction of an autoimmune response to PA28 complex. (J Rheumatol 2004;31:252-9) Key Indexing Terms:
AUTOANTIBODY
From the Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan. Supported by a grant-in-aid for scientific research (no. 13670474) from the Ministry of Education, Science, and Culture of Japan. M. Matsushita, MD; Y. Takasaki, MD; K. Takeuchi, MD; H. Yamada, MD; R. Matsudaira, MD; H. Hashimoto, MD. Address reprint requests to Dr. M. Matsushita, Department of Internal Medicine and Rheumatology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: m-matsu@fa2.so-net.ne.jp Submitted February 11, 2003; revision accepted July 28, 2003. |